A SIRT7-Dependent Acetylation Switch of GABPβ1 Controls Mitochondrial Function

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

doi:10.1016/j.cmet.2014.08.001

Cited by 232 publications

(272 citation statements)

References 49 publications

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“…Mitochondrial dysfunction and cardiac failure were recently described in aged Sirt7 −/− mice. 45 Loss of Sirt7 also results in increased p53 acetylation in the cardiomyocytes of aged Sirt7 −/− mice, 10 which enhances apoptosis and increases fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway

et al. 2015

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Background— Sirt7, 1 of the 7 members of the mammalian sirtuin family, promotes oncogenic transformation. Tumor growth and metastasis require fibrotic and angiogenic responses. Here, we investigated the role of Sirt7 in cardiovascular tissue repair process. Methods and Results— In wild-type mice, Sirt7 expression increased in response to acute cardiovascular injury, including myocardial infarction and hind-limb ischemia, particularly at the active wound healing site. Compared with wild-type mice, homozygous Sirt7-deficient (Sirt7 −/− ) mice showed susceptibility to cardiac rupture after myocardial infarction, delayed blood flow recovery after hind-limb ischemia, and impaired wound healing after skin injury. Histological analysis showed reduced fibrosis, fibroblast differentiation, and inflammatory cell infiltration in the border zone of infarction in Sirt7 −/− mice. In vitro, Sirt7 −/− mouse–derived or Sirt7 siRNA–treated cardiac fibroblasts showed reduced transforming growth factor-β signal activation and low expression levels of fibrosis-related genes compared with wild-type mice–derived or control siRNA–treated cells. These changes were accompanied by reduction in transforming growth factor receptor I protein. Loss of Sirt7 activated autophagy in cardiac fibroblasts. Transforming growth factor-β receptor I downregulation induced by loss of Sirt7 was blocked by autophagy inhibitor, and interaction of Sirt7 with protein interacting with protein kinase-Cα was involved in this process. Conclusion— Sirt7 maintains transforming growth factor receptor I by modulating autophagy and is involved in the tissue repair process.

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Section: Discussionmentioning

confidence: 99%

Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway

et al. 2015

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“…Deficiency of SIRT7 has been linked to several pathologies including cardiac hypertrophy (Vakhrusheva et al , 2008b; Ryu et al , 2014), hepatic steatosis (Shin et al , 2013; Ryu et al , 2014), and deafness (Ryu et al , 2014). SIRT7 has been functionally linked to transcriptional regulation.…”

Section: Introductionmentioning

confidence: 99%

SIRT 7 promotes genome integrity and modulates non‐homologous end joining DNA repair

et al. 2016

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Sirtuins, a family of protein deacetylases, promote cellular homeostasis by mediating communication between cells and environment. The enzymatic activity of the mammalian sirtuin SIRT7 targets acetylated lysine in the N‐terminal tail of histone H3 (H3K18Ac), thus modulating chromatin structure and transcriptional competency. SIRT7 deletion is associated with reduced lifespan in mice through unknown mechanisms. Here, we show that SirT7‐knockout mice suffer from partial embryonic lethality and a progeroid‐like phenotype. Consistently, SIRT7‐deficient cells display increased replication stress and impaired DNA repair. SIRT7 is recruited in a PARP1‐dependent manner to sites of DNA damage, where it modulates H3K18Ac levels. H3K18Ac in turn affects recruitment of the damage response factor 53BP1 to DNA double‐strand breaks (DSBs), thereby influencing the efficiency of non‐homologous end joining (NHEJ). These results reveal a direct role for SIRT7 in DSB repair and establish a functional link between SIRT7‐mediated H3K18 deacetylation and the maintenance of genome integrity.

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“…In their study, Sirt7 KO mice fed a chow diet develop fatty liver because of reduced suppression of ER stress [21]. Notably, however, the expression of ER stress-related genes was not increased in livers of our Sirt7 KO mice (unpublished data) or another line of Sirt7-deficient mice [22]. GA-binding protein (GABP) is a nuclear transcription factor that is important for mitochondrial biogenesis and function.…”

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confidence: 69%

“…Ryu et al found that SIRT7 deacetylates GABPb1, facilitating its transcriptional activation through complex formation with GABPa. They also reported that aged (42 weeks old) Sirt7 KO mice exhibit hepatic microvesicular steatosis because of mitochondrial dysfunction [22]. As we mainly examined young (11-17 weeks of age) Sirt7 KO mice fed an HFD, it is necessary to investigate hepatic lipid accumulation in aged Sirt7 KO mice.…”

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confidence: 99%