A SIRT7-dependent acetylation switch of GABPβ1 controls mitochondrial function

Dongryeol Ryu, Young Suk Jo, Giuseppe Lo Sasso, Sokrates Stein, Hongbo Zhang, Alessia Perino, Jung Uee Lee, Massimo Zeviani, Raymond Romand, Michael O. Hottiger, Kristina Schoonjans, Johan Auwerx

Research output: Contribution to journalArticlepeer-review


Mitochondrial activity is controlled by proteins encoded by both nuclear and mitochondrial DNA. Here, we identify Sirt7 as a crucial regulator of mitochondrial homeostasis. Sirt7 deficiency in mice induces multisystemic mitochondrial dysfunction, which is reflected by increased blood lactate levels, reduced exercise performance, cardiac dysfunction, hepatic microvesicular steatosis, and age-related hearing loss. This link between SIRT7 and mitochondrial function is translatable in humans, where SIRT7 overexpression rescues the mitochondrial functional defect in fibroblasts with a mutation in NDUFSI. These wide-ranging effects of SIRT7 on mitochondrial homeostasis are the consequence of the deacetylation of distinct lysine residues located in the hetero- and homodimerization domains of GABPβ1, a master regulator of nuclear-encoded mitochondrial genes. SIRT7-mediated deacetylation of GABPβ1 facilitates complex formation with GABPα and the transcriptional activation of the GABPα/GABPβ heterotetramer. Altogether, these data suggest that SIRT7 is a dynamic nuclear regulator of mitochondrial function through its impact on GABPβ1 function.

Original languageEnglish
Pages (from-to)856-869
Number of pages14
JournalCell Metabolism
Issue number5
Publication statusPublished - Nov 4 2014

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology


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