Dataset Information

Ablation of Sirtuin5 in the postnatal mouse heart results in persistent accumulation of protein succinylation and normal survival in response to chronic pressure overload

ABSTRACT: 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 to their littermate WT controls. We developed a tamoxifen-inducible, heart-specific SIRT5KO mouse model to determine if the survival phenotype we reported was due to a cardiac-intrinsic or cardiac-extrinsic effect of SIRT5. 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 post 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 in SIRT5KO mice may be dictated by a multi-tissue or prenatal effect of SIRT5.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Paul Grimsrud

LAB HEAD: Matthew D. Hirschey

PROVIDER: PXD008728 | Pride | 2018-05-16

REPOSITORIES: Pride

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			Action	DRS
	2017-09-20_HsSIRT5KO_TMT10_InputF1_KAH_2017-09-12.raw	Raw
	2017-09-20_HsSIRT5KO_TMT10_InputF2_KAH_2017-09-12.raw	Raw
	2017-09-20_HsSIRT5KO_TMT10_InputF3_KAH_2017-09-12.raw	Raw
	2017-09-20_HsSIRT5KO_TMT10_InputF4_KAH_2017-09-12.raw	Raw
	2017-09-20_HsSIRT5KO_TMT10_InputF5_KAH_2017-09-12.raw	Raw

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Ablation of <i>Sirtuin5</i> in the postnatal mouse heart results in protein succinylation and normal survival in response to chronic pressure overload.

Hershberger Kathleen A KA Abraham Dennis M DM Liu Juan J Locasale Jason W JW Grimsrud Paul A PA Hirschey Matthew D MD

The Journal of biological chemistry 20180516 27

Mitochondrial Sirtuin 5 (SIRT5) is an NAD<sup>+</sup>-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 phe ...[more]

PMID: 29769314

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