Skip to content
naulon
Get started

No retraction, correction or concern found when last checked on Oct 24, 2026.

Mitochondrial Dysfunction and Aging: Insights from the Analysis of Extracellular Vesicles

Anna Picca, Flora Guerra, Riccardo Calvani and 7 more

International Journal of Molecular Sciences · 2019 · Review

doi:10.3390/ijms20040805

Abstract

The progressive decline of cell function and integrity, manifesting clinically as increased vulnerability to adverse outcomes and death, is core to biological aging. Mitochondrial dysfunction, oxidative stress, altered intercellular communication (including chronic low-grade inflammation), genomic instability, telomere attrition, loss of proteostasis, altered nutrient sensing, epigenetic alterations, and stem cell exhaustion have been proposed as hallmarks of aging. These “aging pillars” are not mutually exclusive, making the matter intricate and leaving numerous unanswered questions. The characterization of circulating extracellular vesicles (EVs) has recently allowed specific secretory phenotypes associated with aging to be identified. As such, EVs may serve as novel biomarkers for capturing the complexity of aging. Besides the mitochondrial–lysosomal axis, EV trafficking has been proposed as an additional layer in mitochondrial quality control. Indeed, disruption of the mitochondrial–lysosomal axis coupled with abnormal EV secretion may play a role in the pathogenesis of aging and several disease conditions. Here, we discuss (1) the mechanisms of EV generation; (2) the relationship between the mitochondrial–lysosomal axis and EV trafficking in the setting of mitochondrial quality control; and (3) the prospect of using EVs as aging biomarkers and as delivery systems for therapeutics against age-related conditions.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 24, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

Aging is marked by multiple biological disarrangements that increase the risk of developing several chronic diseases (e.g., cardiovascular disease, diabetes, cancer, and neurodegeneration) and functional decline, which both contribute to negative health-related events (e.g., poor quality of life, morbidity, disability, loss of independence, institutionalization, death). Such a scenario well depicts the urge of untangling the determinants of aging for devising strategies able to extend healthspan and foster active aging.

Nine biological processes have recently been proposed as “aging pillars”: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.

The garbage catastrophe theory of aging holds that the loss of efficiency of cellular quality control mechanisms, especially autophagy, results in the progressive accumulation of intracellular “waste”, including protein aggregates, damaged mitochondria and lipofuscin, that further depresses cell recycling processes and homeostasis. While extracellular components are delivered and degraded into lysosomes via endocytic pathway, cytosolic materials, including dysfunctional mitochondria, are directed to lysosomes via autophagy, the main intracellular recycling machinery.

Emerging evidence indicates that in settings of incomplete mitochondrial depolarization, cells can remove unwanted materials and damaged organelles through their release into the extracellular compartment via specialized vesicles. Extracellular vesicles (EVs) can shuttle among cells and the delivery of their cargo can produce beneficial or detrimental effects on neighboring cells, depending on the nature of the transported materials. As such, EVs have been advocated as biomarkers for capturing aging complexity. A great deal of work in preclinical models supports the hypothesis that interventions targeting cellular quality control and EV trafficking may extend health- and lifespan. A new generation of clinical trials is highly sought after to validate this hypothesis in humans.

2. Biogenesis and Characterization of Extracellular Vesicles

EVs were initially considered to be fragments or artifacts of dead and degenerated cells. Subsequently, it was demonstrated that they are mediators of cellular communication with critical roles in cell physiology and pathology.

Although the identification and characterization of EVs are still challenging, they have been distinguished in exosomes and ectosomes based on their biogenesis. In 1991, Stein and Luzio coined the term ectosome referring to structures generated by ectocytosis, the shedding of vesicles from the plasma membrane of stimulated neutrophils. Nowadays, ectosomes are referred to as EVs (diameter 100–500 nm) generated by all cells and identified with various terms: shedding vesicles, microvesicles, exosome-like vesicles, nanoparticles, microparticles, and oncosomes. Exosomes were initially identified as a type of vesicle released from the plasma membrane during the maturation of reticulocytes. The same term has also been used to refer to a molecular machinery involved in RNA processing.

Currently, exosomes are referred to as EVs of endosomal origin with a diameter of 50–150 nm. Exosome precursors are intraluminal vesicles (ILVs), generated by the inward budding of discrete domains of the membrane of early endosomes, subsequently evolving into multivesicular bodies (MVBs). MVBs usually pursue a degradative pathway via their direction to lysosomes. However, under appropriate stimulation, MVBs can move towards the plasma membrane to undergo exocytic fusion followed by release of their ILVs (i.e., exosomes) into the extracellular space.

A molecular machinery, named endosomal sorting complex required for transport (ESCRT), is activated during local membrane remodeling (e.g., viral budding, cytokinesis, autophagy) and is involved in MVBs biogenesis. Intracellular translocation and fusion of MVBs are under the control of several G proteins [e.g., Ras Like-1 (RAL1), Ras-related protein in Brain (RAB)27A and RAB27B]. In particular, RAB7A is a key regulator of late endocytic traffic that controls exosome production in melanoma cell lines, human breast adenocarcinoma MCF7 cells, ovarian cancer cells under hypoxic conditions, and chemoresistant cervical cell lines. Once released, EVs navigate the extracellular space and reach target cells to regulate physiological (e.g., organismal development, immune response, neuronal communication, tissue repair) or pathological processes (e.g., tumor and neurodegenerative disease progression).

EV cargoes include proteins, RNAs (mRNAs, miRNAs, and non-coding RNAs), and short DNA sequences that are relevant for the maintenance of cell homeostasis and survival, regulation of cell functions, and intercellular communication. EVs can activate signaling pathways in target cells also upon their binding to plasma membrane or interaction with intracellular enzymes and factors. Furthermore, EVs can regulate gene expression by modulating the activity of transcription factors, signaling proteins and enzymes. Finally, stem cells can generate EVs to favor angiogenesis and organ regeneration.

A poorly investigated aspect of EVs pertains the transport of mitochondria or their components. Mitochondrial mtDNA (mtDNA) fragments have been identified within the exosomal cargo in astrocytes and myoblasts. Furthermore, larger vesicles (70–150 nm) containing mitochondrial particles in addition to mtDNA are released by mesenchymal stem cells and astrocytes in response to oxidative stress. Though, the role of mitochondrial components outside the cells and the mechanisms of their loading into vesicles are not yet completely deciphered. Indeed, mtDNA may be released in the blood independent of its incorporation into EVs.

Recently, Sansone et al. identified a full mitochondrial genome in circulating EVs from patients with hormonal therapy-resistant metastatic breast cancer. The authors proposed a role for mtDNA horizontal transfer in mediating cancer resistance to therapy. Indeed, acquisition of EV-mediated mtDNA, especially in cancer stem-like cells, was associated with restoration of oxidative phosphorylation. Furthermore, the cancer cells most capable of producing EVs containing packaged mtDNA were those able to quickly reprogram their metabolism in response to oxidative stress, which contributed to endocrine therapy resistance.

Much less is known about exosome signaling in the context of aging. Only a few studies have characterized the secretory pathways of senescent cells and found specific senescence-associated secretory phenotypes (SASPs). However, due to the pivotal role of mitochondrial dysfunction in the aging process, the chase for mitochondrial components within EVs may hold promise for the identification of novel biomarkers for age-related phenomena.

In the next paragraph, we discuss major mechanisms involved in preserving mitochondrial homeostasis and preventing their impairment during aging. A special focus is dedicated to the emerging role of the mitochondrial–lysosomal axis in the generation of EVs for disposing dysfunctional organelles.

3. The Emerging Role of the Mitochondrial–Lysosomal Axis in Mitochondrial Quality Control

Mitochondria make up about one fifth of cell volume. These organelles are crucial modulators of cell metabolism and control several other activities (e.g., calcium and iron buffering, iron–sulfur cluster and heme biosynthesis, and programmed cell death).

Mitochondrial biogenesis is the process that ensures the number of organelles meets cellular energy demands and is accomplished via coordinated nucleus–mitochondrion crosstalk. Mitochondrial mass decreases during aging as a consequence of reduced mitochondriogenesis. However, mitochondrial replenishment would not be as efficient if damaged organelles are not adequately disposed. Appropriate mitochondrial quality control (MQC) processes (i.e., mitochondrial proteostasis, dynamics, and autophagy) are therefore in place to guarantee organelle homeostasis.

Mitochondria are plastic organelles undergoing continuous cycles of fusion and fission that preserve their shape and dilute damage along the network. Besides this, functional mitochondrial dynamics prepare organelles for disposal through their segregation from the mitochondrial network. Severely damaged mitochondria are fissioned and cleared through mitophagy, a highly selective form of autophagy. When operating at its full capacity, this process allows mitochondrial quality within the cell to be maintained. Instead, a decline in MQC efficiency occurs during aging and in the setting of chronic degenerative conditions.

Albeit long envisioned as standalone organelles, mitochondria are not floating entities within cytoplasm; rather, they are organized in a dynamic network with several cellular compartments via membrane contact sites and tethering molecules. In particular, connections between the endoplasmic reticulum and mitochondria regulate a number of processes, including calcium homeostasis, lipid trafficking, mitochondrial morphology, cell death, immune response, and autophagosome formation. Furthermore, the interplay between mitochondria and peroxisomes via mitochondrial delivery systems modulates metabolic and redox signaling pathways.

Recently, functional connections between lysosomes and mitochondria have also been described. Indeed, defects in one of the two organelles are able to induce impairments in the other, thereby suggesting the existence of a mitochondrial–lysosomal axis. For instance, ablation of the mitochondrial transcription factor A (TFAM), which is involved in mitochondrial replication, transcription and maintenance, increases the number of lysosomes in T cells. However, lysosomal activity is impaired as a consequence of deficient mitochondrial respiration and the disruption of endolysosomal trafficking. This culminates in the accumulation of sphingomyelin and autophagy intermediates, eventually triggering an inflammatory response.

Genetic ablation or pharmacological inhibition of apoptosis inducing factor (AIF), optic atrophy-1 (OPA1) or phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) in neurons alters lysosome morphology and activity, thereby inducing accumulation of autophagic substrates. More recently, activation of the lysosomal mechanistic target of rapamycin complex 1 (mTORC1) has been reported to couple nutrient availability to mitochondrial activity and mtDNA replication in neurons, a process termed nutrient-induced mitochondrial activity (NiMA). Amyloid-β oligomers (AβOs), the precursors of amyloid plaques, block insulin- and amino acid-regulated mitochondrial function, which stimulates mTORC1 activity at the plasma membrane but not at the lysosomal surface followed by cell cycle re-entry and neuronal death. AβOs halt NiMA also in a tau-dependent manner, since tau protein is essential for selective activation of mTORC1 at the plasma membrane by AβOs. These two parallel and interconnected signaling routes initiated by AβOs eventually result in mitochondrial dysfunction, which contributes to neuronal loss in Alzheimer’s disease (AD).

Furthermore, restoration of lysosomal acidity using lysosome-targeted nanoparticles has been shown to reinstate mitophagy in pancreatic β cells exposed to high concentrations of free fatty acids. This indicates that, at least under lipotoxic conditions, mitochondrial dysfunction is downstream of lysosomal alkalization and that recovery of lysosomal acidity restores MQC.

Mitochondrial-derived vesicles (MDVs) have been proposed as an additional means through which organelle components can be delivered to lysosomes for MQC. The presence of mitochondrial constituents within exosomes is an indirect evidence of crosstalk between mitochondria and the endolysosomal system. This shuttle system does not require mitochondrial depolarization, autophagy signaling or mitochondrial fission. Indeed, MDVs are generated also in cells lacking autophagy-related gene (Atg) 5, Beclin-1 or Rab9 as well as after silencing of dynamin-related protein 1 (DRP1). As a whole, these findings indicate that MDV delivery to lysosomes for degradation complements mitophagy for MQC.

A fine-tuned coordination between mitophagy and MDV generation has been hypothesized. According to this view, mitophagy would represent an extreme attempt to maintain cell homeostasis through degradation of dysfunctional mitochondria, while MDV generation would be an alternative route to dispose mitochondrial components, before whole-sale organelle degradation is triggered. The fate of a damaged mitochondrion would, therefore, depend on the degree of organelle dysfunction. Indeed, lysosomal delivery of MDV seems to occur as an early response to oxidative stress. Conversely, severely damaged mitochondria releasing pro-apoptotic factors and oxidants are fissioned and targeted for elimination through mitophagy (Figure 1). Albeit the mechanisms of MDVs generation are unclear, their biogenesis seems to proceed independently of DRP1 and to require priming of PINK1 and Parkin. Via this route, large double-membrane vesicles enriched with mitochondrial matrix cargoes are released. Notably, PINK1 and Parkin represent a point of convergence for MDVs generation and mitophagy. Indeed, MDV extrusion into the extracellular milieu has been proposed as an additional layer of protection when mitophagy is compromised or overwhelmed.

Although largely indirect, the available evidence suggests that mitochondrial dysfunction during aging may primarily arise from altered MDV trafficking and defective mitophagy. Unveiling the mechanisms of MQC failure is therefore actively sought after to identify novel biological targets for anti-aging interventions.

4. Extracellular Vesicle Trafficking and Aging

In vitro and animal studies suggest that age-related intracellular accumulation of noxious macromolecules and organelles is primarily caused by a loss of efficiency of degradative pathways. Initial evidence indicates that quality control processes are altered also during human aging. Indeed, Lipinski et al. found abnormal transcript levels of key autophagy mediators (Atg5 and Atg7) in the brain of older people. Furthermore, reduced expression of microtubule-associated protein 1 light chain 3B (LC3B) has been retrieved in the vastus lateralis muscle of older hip-fractured patients with sarcopenia.

While senescence is associated with increased exosome secretion upon activation of p53, EV concentration decreases during aging. Interestingly, EVs are taken up by B cells faster in older people than younger adults, suggesting that, during aging, circulating EV levels might be reduced as a result of enhanced internalization by immune cells.

Recent evidence indicates that EVs released by senescent cells may promote cancer cell proliferation and vascular calcification, while reducing bone formation. Increased secretion of EV-associated nuclear DNA by senescent cells has also been reported. These genome fragments are pro-inflammatory and contribute to inflamm-aging. Circulating levels of mtDNA molecules increase progressively past the age of 50 and have been associated with chronic low-grade inflammation. Indeed, exposure of monocytes to mtDNA concentrations similar to those detected in vivo induces tumor necrosis factor-α production. In neutrophils, blockade of TFAM-mediated rerouting of oxidized mtDNA to lysosomes is followed by extrusion of oxidized nucleoids that eventually trigger interferon I activation. However, whether cell-free circulating mtDNA is contained within EVs is currently unclear.

An additional link between mitochondrial dysfunction and systemic inflammation is mediated by the nucleotide-binding and leucine-rich repeat receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome. NLRP3 inflammasome activity is blunted by autophagy and stimulated by mitochondrial-generated reactive oxygen species (ROS). In turn, NLRP3-dependent engagement of caspase-1 blocks mitophagy, thereby reducing the clearance of ROS-producing damaged mitochondria and, hence, reinforcing inflammasome activation. In the context of sustained defective mitophagy, the accrual of dysfunctional mitochondria may eventually result in the extrusion of MDVs stimulating an inflammatory response. Conversely, when autophagy is fully working NLRP3-induced mtDNA release into the cytosol is inhibited, which mitigates inflammation.

Dysfunctional mitochondrial–lysosomal axis in conjunction with abnormal EV trafficking has recently been involved in the pathogenesis of neurodegenerative diseases, including AD, Parkinson’s disease, and Huntington disease. During neurodegeneration, mitochondrial dysfunction resulting from defective mitophagy contributes to synaptic disruption and neuronal loss by promoting accumulation of misfolded proteins (e.g., amyloid β, hungtintin, tau, alpha-synuclein) through increased oxidative damage and impaired bioenergetics. In such a context, EV trafficking may have neuroprotective or detrimental effects depending on the origin and composition of vesicles. Indeed, MVBs can follow two alternative fates: some are delivered to lysosomes for degradation, therefore promoting clearance of cellular waste, while others fuse with the plasma membrane to release ILVs into the extracellular space as exosomes. This second route may allow delivery of misfolded and harmful proteins to neighboring cells through a prion-like mechanism, thereby contributing to disease progression.

The broad spectrum of molecules packaged within exosomes and secreted into body fluids makes them valuable biomarkers for identifying and tracking several disease conditions. Furthermore, the characterization of exosomal pathways holds promise as a platform for developing novel therapeutic interventions. Indeed, due to their ability to cross the blood–brain barrier, exosomes might be used to deliver drugs directly into the central nervous system. The low immunogenic potential of exosomes and their prion-like behavior also render these vesicles ideal nanodelivery systems for RNAi therapy and immunotherapy. Eventually, technological advancements in biofluidics and informatics may allow EVs to be harnessed as "liquid biopsies" for personalized medicine and delivery systems for precision medicine.

5. Conclusions

Substantial evidence supports the existence of a mitochondrial–lysosomal axis acting in synergy with other cellular quality control systems. The age-related breach in general and selective autophagy impairs the removal of damaged cellular components, including dysfunctional mitochondria, that therefore need to be disposed of otherwise. In such a context, mitochondria may feed EV trafficking via an endolysosomal delivery system. Disruption of the mitochondrial–lysosomal axis coupled with abnormal EV secretion has been implicated as a mechanism contributing to the aging process as well as to a wide range of disease conditions. However, the knowledge of the mechanisms responsible for the coordination between EV trafficking and the mitochondrial–lysosomal axis is still fuzzy. Understanding the molecular actors involved in such a process may eventually allow developing innovative anti-aging remedies and personalized interventions against disease conditions associated with altered cellular quality control.

References 103

  1. 1.

    Landi F., Calvani R., Cesari M., Tosato M., Maria Martone A., Ortolani E., Savera G., Salini S., Sisto A., Picca A., et al. Sarcopenia: an overview on current definitions, diagnosis and treatment. Curr. Protein Pept. Sci. 2018;19:633-638.

    Not in our library10.2174/1389203718666170607113459

  2. 2.

    Cesari M., Marzetti E., Thiem U., Pérez-Zepeda M.U., Abellan Van Kan G., Landi F., Petrovic M., Cherubini A., Bernabei R. The geriatric management of frailty as paradigm of “The end of the disease era”. Eur. J. Intern. Med. 2016;31:11-14.

    Not in our library10.1016/j.ejim.2016.03.005

  3. 3.

    López-Otín C., Blasco M.A., Partridge L., Serrano M., Kroemer G. The Hallmarks of Aging. Cell. 2013;153:1194-1217.

    Not in our library10.1016/j.cell.2013.05.039

  4. 4.

    Terman A., Kurz T., Navratil M., Arriaga E.A., Brunk U.T. Mitochondrial turnover and aging of long-lived postmitotic cells: the mitochondrial-lysosomal axis theory of aging. Antioxid. Redox Signal. 2010;12:503-535.

    Not in our library10.1089/ars.2009.2598

  5. 5.
    Autophagy: machinery and regulation · 2016
    No notice
  6. 6.
    Exosomes and Autophagy: Coordinated Mechanisms for the Maintenance of Cellular Fitness · 2014
    No notice
  7. 7.

    Barzilai N., Crandall J.P., Kritchevsky S.B., Espeland M.A. Metformin as a tool to target aging. Cell Metab. 2016;23:1060-1065.

    Not in our library10.1016/j.cmet.2016.05.011

  8. 8.

    Burch J.B., Augustine A.D., Frieden L.A., Hadley E., Howcroft T.K., Johnson R., Khalsa P.S., Kohanski R.A., Li X.L., Macchiarini F., et al. Advances in geroscience: impact on healthspan and chronic disease. J. Gerontol. A Biol. Sci. Med. Sci. 2014;69:S1-S3.

    Not in our library10.1093/gerona/glu041

  9. 9.

    Espeland M.A., Crimmins E.M., Grossardt B.R., Crandall J.P., Gelfond J.A.L., Harris T.B., Kritchevsky S.B., Manson J.E., Robinson J.G., Rocca W.A., et al. Clinical trials targeting aging and age-related multimorbidity. J. Gerontol. A Biol. Sci. Med. Sci. 2017;72:355-361.

    Not in our library10.1093/gerona/glw220

  10. 10.

    Kennedy B.K., Berger S.L., Brunet A., Campisi J., Cuervo A.M., Epel E.S., Franceschi C., Lithgow G.J., Morimoto R.I., Pessin J.E., et al. Geroscience: linking aging to chronic disease. Cell. 2014;159:709-713.

    Not in our library10.1016/j.cell.2014.10.039

  11. 11.
    Interventions to Slow Aging in Humans: Are We Ready? · 2015
    No notice
  12. 12.

    Sierra F. The emergence of geroscience as an interdisciplinary approach to the enhancement of health span and life span. Cold Spring Harb. Perspect. Med. 2016;6:a025163.

    Not in our library10.1101/cshperspect.a025163

  13. 13.

    Schifferli J.A. Microvesicles are messengers. Semin. Immunopathol. 2011;33:393-394.

    Not in our library10.1007/s00281-011-0276-6

  14. 14.

    Mause S.F., Weber C. Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ. Res. 2010;107:1047-1057.

    Not in our library10.1161/circresaha.110.226456

  15. 15.

    Yoon Y.J., Kim O.Y., Gho Y.S. Extracellular vesicles as emerging intercellular communicasomes. BMB Rep. 2014;47:531-539.

    Not in our library10.5483/bmbrep.2014.47.10.164

  16. 16.

    Stein J.M., Luzio J.P. Ectocytosis caused by sublytic autologous complement attack on human neutrophils. The sorting of endogenous plasma-membrane proteins and lipids into shed vesicles. Biochem. J. 1991;274:381-386.

    Not in our library10.1042/bj2740381

  17. 17.

    Johnstone R.M., Adam M., Hammond J.R., Orr L., Turbide C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem. 1987;262:9412-9420.

    Not in our library

  18. 18.

    Mitchell P., Petfalski E., Shevchenko A., Mann M., Tollervey D. The exosome: a conserved eukaryotic RNA processing complex containing multiple 3′–>5′ exoribonucleases. Cell. 1997;91:457-466.

    Not in our library10.1016/s0092-8674(00)80432-8

  19. 19.

    Cocucci E., Meldolesi J. Ectosomes and exosomes: shedding the confusion between extracellular vesicles. Trends Cell Biol. 2015;25:364-372.

    Not in our library10.1016/j.tcb.2015.01.004

  20. 20.

    Heijnen H.F., Schiel A.E., Fijnheer R., Geuze H.J., Sixma J.J. Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood. 1999;94:3791-3799.

    Not in our library

  21. 21.

    Raposo G., Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J. Cell Biol. 2013;200:373-383.

    Not in our library10.1083/jcb.201211138

  22. 22.

    Raposo G., Nijman H.W., Stoorvogel W., Liejendekker R., Harding C.V., Melief C.J., Geuze H.J. B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 1996;183:1161-1172.

    Not in our library10.1084/jem.183.3.1161

  23. 23.

    Colombo M., Raposo G., Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 2014;30:255-289.

    Not in our library10.1146/annurev-cellbio-101512-122326

  24. 24.

    Colombo M., Moita C., van Niel G., Kowal J., Vigneron J., Benaroch P., Manel N., Moita L.F., Théry C., Raposo G. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J. Cell Sci. 2013;126:5553-5565.

    Not in our library10.1242/jcs.128868

  25. 25.

    Hyenne V., Apaydin A., Rodriguez D., Spiegelhalter C., Hoff-Yoessle S., Diem M., Tak S., Lefebvre O., Schwab Y., Goetz J.G., et al. RAL-1 controls multivesicular body biogenesis and exosome secretion. J. Cell Biol. 2015;211:27-37.

    Not in our library10.1083/jcb.201504136

  26. 26.

    Ostrowski M., Carmo N.B., Krumeich S., Fanget I., Raposo G., Savina A., Moita C.F., Schauer K., Hume A.N., Freitas R.P., et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol. 2010;12:19-30.

    Not in our library10.1038/ncb2000

  27. 27.
    Multiple Roles of the Small GTPase Rab7 · 2016
    No notice
  28. 28.

    Peinado H., Alečković M., Lavotshkin S., Matei I., Costa-Silva B., Moreno-Bueno G., Hergueta-Redondo M., Williams C., García-Santos G., Ghajar C., et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat. Med. 2012;18:883-891.

    Not in our library10.1038/nm.2753

  29. 29.

    Baietti M.F., Zhang Z., Mortier E., Melchior A., Degeest G., Geeraerts A., Ivarsson Y., Depoortere F., Coomans C., Vermeiren E., et al. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat. Cell Biol. 2012;14:677-685.

    Not in our library10.1038/ncb2502

  30. 30.

    Dorayappan K.D.P., Wanner R., Wallbillich J.J., Saini U., Zingarelli R., Suarez A.A., Cohn D.E., Selvendiran K. Hypoxia-induced exosomes contribute to a more aggressive and chemoresistant ovarian cancer phenotype: a novel mechanism linking STAT3/Rab proteins. Oncogene. 2018;37:3806-3821.

    Not in our library10.1038/s41388-018-0189-0

  31. 31.

    Guerra F., Paiano A., Migoni D., Girolimetti G., Perrone A.M., De Iaco P., Fanizzi F.P., Gasparre G., Bucci C. Modulation of RAB7A Protein expression determines resistance to cisplatin through late endocytic pathway impairment and extracellular vesicular secretion. Cancers. 2019;11:52.

    Not in our library10.3390/cancers11010052

  32. 32.

    Korkut C., Ataman B., Ramachandran P., Ashley J., Barria R., Gherbesi N., Budnik V. Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless. Cell. 2009;139:393-404.

    Not in our library10.1016/j.cell.2009.07.051

  33. 33.

    Robbins P.D., Morelli A.E. Regulation of immune responses by extracellular vesicles. Nat. Rev. Immunol. 2014;14:195-208.

    Not in our library10.1038/nri3622

  34. 34.
    Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte–Neuron Communication · 2013
    No notice
  35. 35.

    Lai R.C., Arslan F., Lee M.M., Sze N.S.K., Choo A., Chen T.S., Salto-Tellez M., Timmers L., Lee C.N., El Oakley R.M., et al. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010;4:214-222.

    Not in our library10.1016/j.scr.2009.12.003

  36. 36.

    Al-Nedawi K., Meehan B., Rak J. Microvesicles: messengers and mediators of tumor progression. Cell Cycle. 2009;8:2014-2018.

    Not in our library10.4161/cc.8.13.8988

  37. 37.

    Bellingham S.A., Guo B.B., Coleman B.M., Hill A.F. Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases? Front. Physiol. 2012;3:124.

    Not in our library10.3389/fphys.2012.00124

  38. 38.

    Vyas N., Dhawan J. Exosomes: mobile platforms for targeted and synergistic signaling across cell boundaries. Cell Mol. Life Sci. 2017;74:1567-1576.

    Not in our library10.1007/s00018-016-2413-9

  39. 39.
    Cells release subpopulations of exosomes with distinct molecular and biological properties · 2016
    No notice
  40. 40.
    Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction · 2016
    No notice
  41. 41.
    Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes · 2013
    No notice
  42. 42.

    Yáñez-Mó M., Siljander P.R.-M., Andreu Z., Zavec A.B., Borràs F.E., Buzas E.I., Buzas K., Casal E., Cappello F., Carvalho J., et al. Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles. 2015;4:27066.

    Not in our library10.3402/jev.v4.27066

  43. 43.

    Montecalvo A., Larregina A.T., Shufesky W.J., Stolz D.B., Sullivan M.L.G., Karlsson J.M., Baty C.J., Gibson G.A., Erdos G., Wang Z., et al. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood. 2012;119:756-766.

    Not in our library10.1182/blood-2011-02-338004

  44. 44.

    Wiklander O.P.B., Nordin J.Z., O’Loughlin A., Gustafsson Y., Corso G., Mäger I., Vader P., Lee Y., Sork H., Seow Y., et al. El Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J. Extracell. Vesicles. 2015;4:26316.

    Not in our library10.3402/jev.v4.26316

  45. 45.

    Newton W.C., Kim J.W., Luo J.Z.Q., Luo L. Stem cell-derived exosomes: a novel vector for tissue repair and diabetic therapy. J. Mol. Endocrinol. 2017;59:R155-R165.

    Not in our library10.1530/jme-17-0080

  46. 46.

    Guescini M., Genedani S., Stocchi V., Agnati L.F. Astrocytes and Glioblastoma cells release exosomes carrying mtDNA. J. Neural Transm. 2010;117:1-4.

    Not in our library10.1007/s00702-009-0288-8

  47. 47.

    Guescini M., Guidolin D., Vallorani L., Casadei L., Gioacchini A.M., Tibollo P., Battistelli M., Falcieri E., Battistin L., Agnati L.F., et al. C2C12 myoblasts release micro-vesicles containing mtDNA and proteins involved in signal transduction. Exp. Cell Res. 2010;316:1977-1984.

    Not in our library10.1016/j.yexcr.2010.04.006

  48. 48.
    Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs · 2015
    No notice
  49. 49.

    Hayakawa K., Esposito E., Wang X., Terasaki Y., Liu Y., Xing C., Ji X., Lo E.H. Transfer of mitochondria from astrocytes to neurons after stroke. Nature. 2016;535:551-555.

    Not in our library10.1038/nature18928

  50. 50.

    Helmig S., Frühbeis C., Krämer-Albers E.-M., Simon P., Tug S. Release of bulk cell free DNA during physical exercise occurs independent of extracellular vesicles. Eur. J. Appl. Physiol. 2015;115:2271-2280.

    Not in our library10.1007/s00421-015-3207-8

  51. 51.

    Sansone P., Savini C., Kurelac I., Chang Q., Amato L.B., Strillacci A., Stepanova A., Iommarini L., Mastroleo C., Daly L., et al. Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer. Proc. Natl. Acad. Sci. USA. 2017;114:E9066-E9075.

    Not in our library10.1073/pnas.1704862114

  52. 52.

    Coppé J.-P., Desprez P.-Y., Krtolica A., Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 2010;5:99-118.

    Not in our library10.1146/annurev-pathol-121808-102144

  53. 53.

    Nunnari J., Suomalainen A. Mitochondria: in sickness and in health. Cell. 2012;148:1145-1159.

    Not in our library10.1016/j.cell.2012.02.035

  54. 54.

    Picca A., Fracasso F., Pesce V., Cantatore P., Joseph A.-M., Leeuwenburgh C., Gadaleta M.N., Lezza A.M.S. Age- and calorie restriction-related changes in rat brain mitochondrial DNA and TFAM binding. Age. 2013;35:1607-1620.

    Not in our library10.1007/s11357-012-9465-z

  55. 55.

    Picca A., Pesce V., Fracasso F., Joseph A.-M., Leeuwenburgh C., Lezza A.M.S. Aging and calorie restriction oppositely affect mitochondrial biogenesis through TFAM binding at both origins of mitochondrial DNA replication in rat liver. PLoS ONE. 2013;8:1-14.

    Not in our library10.1371/journal.pone.0074644

  56. 56.

    Picca A., Pesce V., Fracasso F., Joseph A.-M., Leeuwenburgh C., Lezza A.M.S. A comparison among the tissue-specific effects of aging and calorie restriction on TFAM amount and TFAM-binding activity to mtDNA in rat. Biochim. Biophys. Acta. 2014;1840:2184-2191.

    Not in our library10.1016/j.bbagen.2014.03.004

  57. 57.

    Klionsky D.J. Why do we need autophagy? A cartoon depiction. Autophagy. 2018;14:739-742.

    Not in our library10.1080/15548627.2018.1446628

  58. 58.

    Twig G., Hyde B., Shirihai O.S. Mitochondrial fusion, fission and autophagy as a quality control axis: The bioenergetic view. Biochim. Biophys. Acta. 2008;1777:1092-1097.

    Not in our library10.1016/j.bbabio.2008.05.001

  59. 59.

    Youle R.J., Narendra D.P. Mechanisms of mitophagy. Nat. Rev. Mol. Cell Biol. 2011;12:9-14.

    Not in our library10.1038/nrm3028

  60. 60.

    Hamasaki M., Furuta N., Matsuda A., Nezu A., Yamamoto A., Fujita N., Oomori H., Noda T., Haraguchi T., Hiraoka Y., et al. Autophagosomes form at ER-mitochondria contact sites. Nature. 2013;495:389-393.

    Not in our library10.1038/nature11910

  61. 61.
    Interaction of Mitochondria with the Endoplasmic Reticulum and Plasma Membrane in Calcium Homeostasis, Lipid Trafficking and Mitochondrial Structure · 2017
    No notice
  62. 62.

    Martinvalet D. The role of the mitochondria and the endoplasmic reticulum contact sites in the development of the immune responses. Cell Death Dis. 2018;9:336.

    Not in our library10.1038/s41419-017-0237-7

  63. 63.

    Prudent J., McBride H.M. The mitochondria-endoplasmic reticulum contact sites: a signalling platform for cell death. Curr. Opin. Cell Biol. 2017;47:52-63.

    Not in our library10.1016/j.ceb.2017.03.007

  64. 64.
    Redox interplay between mitochondria and peroxisomes · 2015
    No notice
  65. 65.
    Interorganelle Communication between Mitochondria and the Endolysosomal System · 2017
    Not checked
  66. 66.

    Baixauli F., Acín-Pérez R., Villarroya-Beltrí C., Mazzeo C., Nuñez-Andrade N., Gabandé-Rodriguez E., Ledesma M.D., Blázquez A., Martin M.A., Falcón-Pérez J.M., et al. Mitochondrial respiration controls lysosomal function during inflammatory T cell responses. Cell Metab. 2015;22:485-498.

    Not in our library10.1016/j.cmet.2015.07.020

  67. 67.

    Picca A., Lezza A.M.S. Regulation of mitochondrial biogenesis through TFAM-mitochondrial DNA interactions. Useful insights from aging and calorie restriction studies. Mitochondrion. 2015;25:67-75.

    Not in our library10.1016/j.mito.2015.10.001

  68. 68.

    Demers-Lamarche J., Guillebaud G., Tlili M., Todkar K., Bélanger N., Grondin M., Nguyen A.P., Michel J., Germain M. Loss of Mitochondrial Function Impairs Lysosomes. J. Biol. Chem. 2016;291:10263-10276.

    Not in our library10.1074/jbc.m115.695825

  69. 69.

    Norambuena A., Wallrabe H., Cao R., Wang D.B., Silva A., Svindrych Z., Periasamy A., Hu S., Tanzi R.E., Kim D.Y., et al. A novel lysosome-to-mitochondria signaling pathway disrupted by amyloid-β oligomers. EMBO J. 2018;37:e100241.

    Not in our library10.15252/embj.2018100241

  70. 70.

    Norambuena A., Wallrabe H., McMahon L., Silva A., Swanson E., Khan S.S., Baerthlein D., Kodis E., Oddo S., Mandell J.W., et al. mTOR and neuronal cell cycle reentry: How impaired brain insulin signaling promotes Alzheimer’s disease. Alzheimers Dement. 2017;13:152-167.

    Not in our library10.1016/j.jalz.2016.08.015

  71. 71.

    Assali E.A., Shlomo D., Zeng J., Taddeo E.P., Trudeau K.M., Erion K.A., Colby A.H., Grinstaff M.W., Liesa M., Las G., et al. Nanoparticle-mediated lysosomal reacidification restores mitochondrial turnover and function in β cells under lipotoxicity. FASEB J. 2018.

    Not in our library10.1096/fj.201801292r

  72. 72.

    Soubannier V., McLelland G.-L., Zunino R., Braschi E., Rippstein P., Fon E.A., McBride H.M. A vesicular transport pathway shuttles cargo from mitochondria to lysosomes. Curr. Biol. 2012;22:135-141.

    Not in our library10.1016/j.cub.2011.11.057

  73. 73.

    McLelland G.-L., Soubannier V., Chen C.X., McBride H.M., Fon E.A. Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. EMBO J. 2014;33:282-295.

    Not in our library10.1002/embj.201385902

  74. 74.
    Reconstitution of Mitochondria Derived Vesicle Formation Demonstrates Selective Enrichment of Oxidized Cargo · 2012
    No notice
  75. 75.

    Roberts R.F., Tang M.Y., Fon E.A., Durcan T.M. Defending the mitochondria: The pathways of mitophagy and mitochondrial-derived vesicles. Int. J. Biochem. Cell Biol. 2016;79:427-436.

    Not in our library10.1016/j.biocel.2016.07.020

  76. 76.

    Desdín-Micó G., Mittelbrunn M. Role of exosomes in the protection of cellular homeostasis. Cell Adh. Migr. 2017;11:127-134.

    Not in our library10.1080/19336918.2016.1251000

  77. 77.

    Lipinski M.M., Zheng B., Lu T., Yan Z., Py B.F., Ng A., Xavier R.J., Li C., Yankner B.A., Scherzer C.R., et al. Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer’s disease. Proc. Natl. Acad. Sci. USA. 2010;107:14164-14169.

    Not in our library10.1073/pnas.1009485107

  78. 78.

    Marzetti E., Calvani R., Lorenzi M., Tanganelli F., Picca A., Bossola M., Menghi A., Bernabei R., Landi F. Association between myocyte quality control signaling and sarcopenia in old hip-fractured patients: Results from the Sarcopenia in HIp FracTure (SHIFT) exploratory study. Exp Gerontol. 2016;80:1-5.

    Not in our library10.1016/j.exger.2016.04.003

  79. 79.

    Yu X., Harris S.L., Levine A.J. The regulation of exosome secretion: a novel function of the p53 protein. Cancer Res. 2006;66:4795-4801.

    Not in our library10.1158/0008-5472.can-05-4579

  80. 80.
    Age-Related Changes in Plasma Extracellular Vesicle Characteristics and Internalization by Leukocytes · 2017
    No notice
  81. 81.
    Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2 · 2017
    No notice
  82. 82.

    Alique M., Ruíz-Torres M.P., Bodega G., Noci M.V., Troyano N., Bohórquez L., Luna C., Luque R., Carmona A., Carracedo J., et al. Microvesicles from the plasma of elderly subjects and from senescent endothelial cells promote vascular calcification. Aging. 2017;9:778-789.

    Not in our library10.18632/aging.101191

  83. 83.

    Weilner S., Keider V., Winter M., Harreither E., Salzer B., Weiss F., Schraml E., Messner P., Pietschmann P., Hildner F., et al. Vesicular Galectin-3 levels decrease with donor age and contribute to the reduced osteo-inductive potential of human plasma derived extracellular vesicles. Aging. 2016;8:16-33.

    Not in our library10.18632/aging.100865

  84. 84.
    Exosomes maintain cellular homeostasis by excreting harmful DNA from cells · 2017
    Corrected
  85. 85.

    Prattichizzo F., Micolucci L., Cricca M., De Carolis S., Mensà E., Ceriello A., Procopio A.D., Bonafè M., Olivieri F. Exosome-based immunomodulation during aging: A nano-perspective on inflamm-aging. Mech. Ageing Dev. 2017;168:44-53.

    Not in our library10.1016/j.mad.2017.02.008

  86. 86.

    Pinti M., Cevenini E., Nasi M., de Biasi S., Salvioli S., Monti D., Benatti S., Gibellini L., Cotichini R., Stazi M.A., et al. Circulating mitochondrial DNA increases with age and is a familiar trait: Implications for “inflamm-aging”. Eur. J. Immunol. 2014;44:1552-1562.

    Not in our library10.1002/eji.201343921

  87. 87.
    Fueling Inflamm-Aging through Mitochondrial Dysfunction: Mechanisms and Molecular Targets · 2017
    No notice
  88. 88.

    Caielli S., Athale S., Domic B., Murat E., Chandra M., Banchereau R., Baisch J., Phelps K., Clayton S., Gong M., et al. Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus. J. Exp. Med. 2016;213:697-713.

    Not in our library10.1084/jem.20151876

  89. 89.

    Zhou R., Yazdi A.S., Menu P., Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature. 2011;469:221-225.

    Not in our library10.1038/nature09663

  90. 90.

    Saitoh T., Fujita N., Jang M.H., Uematsu S., Yang B.-G., Satoh T., Omori H., Noda T., Yamamoto N., Komatsu M., et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature. 2008;456:264-268.

    Not in our library10.1038/nature07383

  91. 91.

    Ding W., Guo H., Xu C., Wang B., Zhang M., Ding F. Mitochondrial reactive oxygen species-mediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury. Oncotarget. 2016;7:17479-17491.

    Not in our library10.18632/oncotarget.8243

  92. 92.

    Yu J., Nagasu H., Murakami T., Hoang H., Broderick L., Hoffman H.M., Horng T. Inflammasome activation leads to Caspase-1-dependent mitochondrial damage and block of mitophagy. Proc. Natl. Acad. Sci. USA. 2014;111:15514-15519.

    Not in our library10.1073/pnas.1414859111

  93. 93.

    Nakahira K., Haspel J.A., Rathinam V.A.K., Lee S.-J., Dolinay T., Lam H.C., Englert J.A., Rabinovitch M., Cernadas M., Kim H.P., et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat. Immunol. 2011;12:222-230.

    Not in our library10.1038/ni.1980

  94. 94.

    Xiao T., Zhang W., Jiao B., Pan C.-Z., Liu X., Shen L. The role of exosomes in the pathogenesis of Alzheimer’ disease. Transl. Neurodegener. 2017;6:3.

    Not in our library10.1186/s40035-017-0072-x

  95. 95.

    Tofaris G.K. A Critical assessment of exosomes in the pathogenesis and stratification of Parkinson’s disease. J. Parkinsons Dis. 2017;7:569-576.

    Not in our library10.3233/jpd-171176

  96. 96.
    Human-to-mouse prion-like propagation of mutant huntingtin protein · 2016
    No notice
  97. 97.

    Palikaras K., Tavernarakis N. Mitophagy in neurodegeneration and aging. Front. Genet. 2012;3:297.

    Not in our library10.3389/fgene.2012.00297

  98. 98.

    Vingtdeux V., Sergeant N., Buée L. Potential contribution of exosomes to the prion-like propagation of lesions in Alzheimer’s disease. Front. Physiol. 2012;3:229.

    Not in our library10.3389/fphys.2012.00229

  99. 99.

    Qu M., Lin Q., Huang L., Fu Y., Wang L., He S., Fu Y., Yang S., Zhang Z., Zhang L., et al. Dopamine-loaded blood exosomes targeted to brain for better treatment of Parkinson’s disease. J. Control. Release. 2018;287:156-166.

    Not in our library10.1016/j.jconrel.2018.08.035

  100. 100.

    Jarmalavičiūtė A., Pivoriūnas A. Exosomes as a potential novel therapeutic tools against neurodegenerative diseases. Pharmacol. Res. 2016;113:816-822.

    Not in our library10.1016/j.phrs.2016.02.002

  101. 101.

    Mendt M., Kamerkar S., Sugimoto H., McAndrews K.M., Wu C.-C., Gagea M., Yang S., Blanko E.V.R., Peng Q., Ma X., et al. Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight. 2018.

    Not in our library10.1172/jci.insight.99263

  102. 102.

    Anticoli S., Aricò E., Arenaccio C., Manfredi F., Chiozzini C., Olivetta E., Ferrantelli F., Lattanzi L., D’Urso M.T., Proietti E., et al. Engineered exosomes emerging from muscle cells break immune tolerance to HER2 in transgenic mice and induce antigen-specific CTLs upon challenge by human dendritic cells. J. Mol. Med. 2018;96:211-221.

    Not in our library10.1007/s00109-017-1617-2

  103. 103.
    Microfluidics-based on-a-chip systems for isolating and analysing extracellular vesicles · 2018
    Not checked

Cited by papers we hold 10

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.