PXD008728

PXD008728 is an original dataset announced via ProteomeXchange.

Title	Ablation of Sirtuin5 in the postnatal mouse heart results in persistent accumulation of protein succinylation and normal survival in response to chronic pressure overload
Description	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.
HostingRepository	PRIDE
AnnounceDate	2018-05-16
AnnouncementXML	Submission_2018-05-22_05:46:15.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Paul Grimsrud
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	N6-succinyl-L-lysine
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-01-22 01:28:50	ID requested
1	2018-05-16 02:09:45	announced
⏵ 2	2018-05-22 05:46:17	announced	Updated publication reference for PubMed record(s): 29769314.

Hershberger KA, Abraham DM, Liu J, Locasale JW, Grimsrud PA, Hirschey MD, in the postnatal mouse heart results in protein succinylation and normal survival in response to chronic pressure overload. J Biol Chem, 293(27):10630-10645(2018) [pubmed]

curator keyword: Biological

submitter keyword: Sirt5, protein succinylation, heart function

Matthew D. Hirschey
contact affiliation	Associate Professor, Department of Medicine, Division of Endocrinology, Metabolism, and Nutrition, Department of Pharmacology and Cancer Biology Duke University Medical Center
contact email	matthew.hirschey@duke.edu
lab head
Paul Grimsrud
contact affiliation	Duke Molecular Physiology Institute
contact email	paul.grimsrud@duke.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD008728
     1. Label: PRIDE project
     2. Name: Ablation of Sirtuin5 in the postnatal mouse heart results in persistent accumulation of protein succinylation and normal survival in response to chronic pressure overload