A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis

Bong Hyun Ahn, Hyun Seok Kim, Shiwei Song, Hye Lee In, Jie Liu, Athanassios Vassilopoulos, Chu Xia Deng, Toren Finkel

Research output: Contribution to journalArticle

Abstract

Here, we demonstrate a role for the mitochondrial NAD-dependent deacetylase Sirt3 in the maintenance of basal ATP levels and as a regulator of mitochondrial electron transport. We note that Sirt3-/- mouse embryonic fibroblasts have a reduction in basal ATP levels. Reconstitution with wild-type but not a deacetylase-deficient form of Sirt3 restored ATP levels in these cells. Furthermore in wild-type mice, the resting level of ATP correlates with organ-specific Sirt3 protein expression. Remarkably, in mice lacking Sirt3, basal levels of ATP in the heart, kidney, and liver were reduced >50%. We further demonstrate that mitochondrial protein acetylation is markedly elevated in Sirt3-/- tissues. In addition, in the absence of Sirt3, multiple components of Complex I of the electron transport chain demonstrate increased acetylation. Sirt3 can also physically interact with at least one of the known subunits of Complex I, the 39-kDa protein NDUFA9. Functional studies demonstrate that mitochondria from Sirt3-/- animals display a selective inhibition of Complex I activity. Furthermore, incubation of exogenous Sirt3 with mitochondria can augment Complex I activity. These results implicate protein acetylation as an important regulator of Complex I activity and demonstrate that Sirt3 functions in vivo to regulate and maintain basal ATP levels.

Original languageEnglish (US)
Pages (from-to)14447-14452
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number38
DOIs
StatePublished - Sep 23 2008
Externally publishedYes

Fingerprint

Homeostasis
Adenosine Triphosphate
Acetylation
Mitochondria
Electron Transport Complex I
Proteins
Mitochondrial Proteins
Electron Transport
NAD
Fibroblasts
Maintenance
Kidney
Liver

Keywords

  • Acetylation
  • Complex
  • Electron transport
  • Sirtuins

ASJC Scopus subject areas

  • General

Cite this

A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. / Ahn, Bong Hyun; Kim, Hyun Seok; Song, Shiwei; In, Hye Lee; Liu, Jie; Vassilopoulos, Athanassios; Deng, Chu Xia; Finkel, Toren.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 38, 23.09.2008, p. 14447-14452.

Research output: Contribution to journalArticle

Ahn, Bong Hyun ; Kim, Hyun Seok ; Song, Shiwei ; In, Hye Lee ; Liu, Jie ; Vassilopoulos, Athanassios ; Deng, Chu Xia ; Finkel, Toren. / A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 38. pp. 14447-14452.
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