期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 293, 期 27, 页码 10630-10645出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA118.002187
关键词
sirtuin; protein acylation; proteomics; stress; cardiac hypertrophy
资金
- American Heart Association [12SDG8840004, 12IRG9010008]
- NIA, National Institutes of Health [R01AG045351]
- NIDDK, National Institutes of Health [P30DK096493]
- Ruth L. Kirschstein National Service Research Award F31 Predoctoral Fellowship [1F31HL127959-03]
- NIGMS, National Institutes of Health [5T32GM007105-40]
- NHLBI, National Institutes of Health [1K08HL125905-01]
Mitochondrial Sirtuin 5 (SIRT5) is an NAD(+)-dependent demalonylase, desuccinylase, and deglutarylase that controls several metabolic pathways. A number of recent studies point to SIRT5 desuccinylase activity being important in maintaining cardiac function and metabolism under stress. Previously, we described a phenotype of increased mortality in whole-body SIRT5KO mice exposed to chronic pressure overload compared with their littermate WT controls. To determine whether the survival phenotype we reported was due to a cardiac-intrinsic or cardiac-extrinsic effect of SIRT5, we developed a tamoxifen-inducible, heart-specific SIRT5 knockout (SIRT5KO) mouse model. Using our new animal model, we discovered that postnatal cardiac ablation of Sirt5 resulted in persistent accumulation of protein succinylation up to 30 weeks after SIRT5 depletion. Succinyl proteomics revealed that succinylation increased on proteins of oxidative metabolism between 15 and 31 weeks after ablation. Heart-specific SIRT5KO mice were exposed to chronic pressure overload to induce cardiac hypertrophy. We found that, in contrast to whole-body SIRT5KO mice, there was no difference in survival between heart-specific SIRT5KO mice and their littermate controls. Overall, the data presented here suggest that survival of SIRT5KO mice may be dictated by a multitissue or prenatal effect of SIRT5.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据