Ryu 2014 Cell Metab

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Ryu D, Jo YS, Lo Sasso G, Stein S, Zhang H, Perino A, Lee JU, Zeviani M, Romand R, Hottiger MO, Schoonjans K, Auwerx J (2014) A SIRT7-dependent acetylation switch of GABPβ1 controls mitochondrial function. Cell Metab 20:856-69.

» PMID: 25200183 Open access

Ryu D, Jo YS, Lo Sasso G, Stein S, Zhang H, Perino A, Lee JU, Zeviani M, Romand R, Hottiger MO, Schoonjans K, Auwerx J (2014) Cell Metab

Abstract: 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.

Copyright © 2014 Elsevier Inc. All rights reserved.


O2k-Network Lab: CH Lausanne Auwerx J


Labels: MiParea: Respiration, mtDNA;mt-genetics, nDNA;cell genetics, Genetic knockout;overexpression 


Organism: Mouse  Tissue;cell: Heart, Nervous system, Liver, Lung;gill  Preparation: Homogenate 


Coupling state: LEAK, OXPHOS  Pathway: N, S, CIV, NS, Other combinations, ROX  HRR: Oxygraph-2k 

2016-09