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PMID: 20363244 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

Mitochondrial uncoupling and lifespan.

Mechanisms of ageing and development ·Vol. 131 ·No. 7-8 ·2010-00-00 ·Pages 463-72

Mookerjee SA, Divakaruni AS, Jastroch M, Brand MD

Abstract

The quest to understand why we age has given rise to numerous lines of investigation that have gradually converged to include metabolic control by mitochondrial activity as a major player. That is, the ideal balance between nutrient uptake, its transduction into usable energy, and the mitigation of damaging byproducts can be regulated by mitochondrial respiration and output (ATP, reactive oxygen species (ROS), and heat). Mitochondrial inefficiency through proton leak, which uncouples substrate oxidation from ADP phosphorylation, can comprise as much as 30% of the basal metabolic rate. This uncoupling is hypothesized to protect cells from conditions that favor ROS production. Uncoupling can also occur through pharmacological induction of proton leak and activity of the uncoupling proteins. Mitochondrial uncoupling is implicated in lifespan extension through its effects on metabolic rate and ROS production. However, evidence to date does not suggest a consistent role for uncoupling in lifespan. The purpose of this review is to discuss recent work examining how mitochondrial uncoupling impacts lifespan.

MeSH Terms
Adenosine Triphosphate/metabolism Age Factors Aging/metabolism Animals Caloric Restriction Energy Metabolism Glucose/metabolism Humans Insulin/metabolism Longevity Mitochondria/metabolism Mitochondrial Proteins/metabolism Oxidative Stress Reactive Oxygen Species/metabolism
Chemicals
Insulin Mitochondrial Proteins Reactive Oxygen Species Adenosine Triphosphate Glucose
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Mookerjee Shona A
Buck Institute for Age Research, Novato, CA 94945 USA. smookerj@buckinstitute.org
Divakaruni Ajit S
Jastroch Martin
Brand Martin D
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Article Info
Journal
Mechanisms of ageing and development
Abbr.
Mech Ageing Dev
ISSN
1872-6216
DOI
10.1016/j.mad.2010.03.010
Email
smookerj@buckinstitute.org
Published
2010-00-00
Epub
2010-00-02
Pages
463-72
Language
English
Region
Ireland
NLM ID
0347227
PMCID
PMC2924931
Subset
IM
Grants
NIA NIH HHS · PL1 AG032118 · United States
NIA NIH HHS · P01 AG025901 · United States
NIA NIH HHS · PL1 AG032118-01 · United States
NIA NIH HHS · P01 AG025901-01A2 · United States
NIA NIH HHS · R01 AG033542 · United States
NIA NIH HHS · R01 AG033542-01 · United States
NIA NIH HHS · P30 AG025708-01 · United States
NIA NIH HHS · P30 AG025708 · United States
External Links
PubMed source DOI: 10.1016/j.mad.2010.03.010 PMC Full Text View journal details
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