A SIRT7-dependent acetylation switch of GABPβ1 controls mitochondrial function.
- Ryu D Laboratory of Integrative and Systems Physiology, School of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
- Jo YS Laboratory of Integrative and Systems Physiology, School of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland; Division of Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
- Lo Sasso G Laboratory of Integrative and Systems Physiology, School of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
- Stein S Metabolic Signaling, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
- Zhang H Laboratory of Integrative and Systems Physiology, School of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
- Perino A Metabolic Signaling, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
- Lee JU Department of Pathology, Daejeon St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul 137-701, Republic of Korea.
- Zeviani M Unit of Molecular Neurogenetics, the Carlo Besta Institute of Neurology IRCCS, 20133 Milan, Italy; MRC Mitochondrial Biology Unit, Cambridge CB2 0XY, UK.
- Romand R Institut de Génétique et de Biologie Moléculaire et Cellulaire, BP 10142, 67404 Illkirch Cedex, France.
- Hottiger MO Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, 8057 Zurich, Switzerland.
- Schoonjans K Metabolic Signaling, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
- Auwerx J Laboratory of Integrative and Systems Physiology, School of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland. Electronic address: admin.auwerx@epfl.ch.
- 2014-09-10
Published in:
- Cell metabolism. - 2014
Acetylation
Aging
Amino Acid Sequence
Animals
GA-Binding Protein Transcription Factor
Gene Knockout Techniques
Humans
Mice
Mice, Knockout
Mitochondria
Molecular Sequence Data
Sequence Alignment
Sirtuins
English
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.
- Language
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- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1016/j.cmet.2014.08.001
- PMID 25200183
- Persistent URL
- https://sonar.ch/global/documents/228871
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