Hormone‐induced mitochondrial fission is utilized by brown adipocytes as an amplification pathway for energy expenditure

Abstract

Adrenergic stimulation of brown adipocytes (BA) induces mitochondrial uncoupling, thereby increasing energy expenditure by shifting nutrient oxidation towards thermogenesis. Here we describe that mitochondrial dynamics is a physiological regulator of adrenergically‐induced changes in energy expenditure. The sympathetic neurotransmitter Norepinephrine (NE) induced complete and rapid mitochondrial fragmentation in BA, characterized by Drp1 phosphorylation and Opa1 cleavage. Mechanistically, NE‐mediated Drp1 phosphorylation was dependent on Protein Kinase‐A (PKA) activity, whereas Opa1 cleavage required mitochondrial depolarization mediated by FFAs released as a result of lipolysis. This change in mitochondrial architecture was observed both in primary cultures and brown adipose tissue from cold‐exposed mice. Mitochondrial uncoupling induced by NE in brown adipocytes was reduced by inhibition of mitochondrial fission through transient Drp1 DN overexpression. Furthermore, forced mitochondrial fragmentation in BA through Mfn2 knock down increased the capacity of exogenous FFAs to increase energy expenditure. These results suggest that, in addition to its ability to stimulate lipolysis, NE induces energy expenditure in BA by promoting mitochondrial fragmentation. Together these data reveal that adrenergically‐induced changes to mitochondrial dynamics are required for BA thermogenic activation and for the control of energy expenditure.

Cited by papers we hold 13

• Obesity causes mitochondrial fragmentation and dysfunction in white adipocytes due to RalA activation · 2024
  No notice
• An Overview: The Diversified Role of Mitochondria in Cancer Metabolism · 2023
  No notice
• Characterisation of cold-induced mitochondrial fission in porcine aortic endothelial cells · 2022
  Not checked
• Naked mole-rat brown fat thermogenesis is diminished during hypoxia through a rapid decrease in UCP1 · 2021
  Not checked
• The diabetes medication canagliflozin promotes mitochondrial remodelling of adipocyte via the AMPK-Sirt1-Pgc-1α signalling pathway · 2020
  No notice
• Mitochondrial Dynamics: Fission and Fusion in Fate Determination of Mesenchymal Stem Cells · 2020
  No notice
• The Role of Adipose Tissue Mitochondria: Regulation of Mitochondrial Function for the Treatment of Metabolic Diseases · 2019
  No notice
• Mitochondrial fission is associated with UCP1 activity in human brite/beige adipocytes · 2018
  Not checked
• TGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue · 2018
  No notice
• Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox SignalingReviewing Editors: Jerzy Beltowski, Joseph Burgoyne, Gabor Csanyi, Sergey Dikalov, Frank Krause, Anibal Vercesi, and Jeremy Ward · 2018
  No notice
• What is the function of mitochondrial networks? A theoretical assessment of hypotheses and proposal for future research · 2015
  No notice
• Mitochondrial quality control pathways as determinants of metabolic health · 2015
  No notice
• Mitochondrial response to nutrient availability and its role in metabolic disease · 2014
  No notice

Reads

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.