Dataset Information

Comprehensive respiratory phenomics across multiple models of mitochondrial protein hyperacylation reveals a paradoxically marginal impact on bioenergetics

ABSTRACT: Acyl CoA metabolites derived from catabolism of carbon fuels can react with lysine residues of mitochondrial proteins, giving rise to a large family of post-translation modifications (PTMs). Mass spectrometry-based detection of thousands of acyl-PTMs scattered throughout the proteome has established a strong correlative connection between mitochondrial hyperacylation and disease; however, the functional consequences of these modifications remain uncertain. Here, we used a comprehensive respiratory diagnostics platform to evaluate three disparate mouse models of mitochondrial hyperacylation in heart caused by genetic deletion of malonyl CoA decarboxylase (MCD), the SIRT5 demalonylase/desuccinylase, or the SIRT3 deacetylase. In each case, elevated acylation was accompanied by surprisingly marginal respiratory phenotypes. Of the >30 mitochondrial energy fluxes evaluated, the only outcome observed consistently across models was ~15% decrease in ATP synthase activity. In sum, the findings suggest that the vast majority of mitochondrial acyl PTMs occur as stochastic events that have minimal impact on mitochondrial bioenergetics. See Fisher-Wellman et. al. 2018 for further experimental details, reagents, and references.

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Deborah M. Muoio

PROVIDER: PXD011375 | JPOST Repository | Thu Feb 07 00:00:00 GMT 2019

REPOSITORIES: jPOST

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Dataset's files

Source:

			Action	DRS
	2017__0208__KFW__MCD_Hrt_Input_F1_1ug.raw	Raw
	2017__0208__KFW__MCD_Hrt_Input_F2_1ug.raw	Raw
	2017__0208__KFW__MCD_Hrt_Input_F3_1ug.raw	Raw
	2017__0208__KFW__MCD_Hrt_Input_F4_1ug.raw	Raw
	2017__0208__KFW__MCD_Hrt_Input_F5_1ug.raw	Raw

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Publications

Respiratory Phenomics across Multiple Models of Protein Hyperacylation in Cardiac Mitochondria Reveals a Marginal Impact on Bioenergetics.

Fisher-Wellman Kelsey H KH Draper James A JA Davidson Michael T MT Williams Ashley S AS Narowski Tara M TM Slentz Dorothy H DH Ilkayeva Olga R OR Stevens Robert D RD Wagner Gregory R GR Najjar Rami R Hirschey Mathew D MD Thompson J Will JW Olson David P DP Kelly Daniel P DP Koves Timothy R TR Grimsrud Paul A PA Muoio Deborah M DM

Cell reports 20190201 6

Acyl CoA metabolites derived from the catabolism of carbon fuels can react with lysine residues of mitochondrial proteins, giving rise to a large family of post-translational modifications (PTMs). Mass spectrometry-based detection of thousands of acyl-PTMs scattered throughout the proteome has established a strong link between mitochondrial hyperacylation and cardiometabolic diseases; however, the functional consequences of these modifications remain uncertain. Here, we use a comprehensive respi ...[more]

PMID: 30726738

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