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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 respiratory diagnostics platform to evaluate three disparate models of mitochondrial hyperacylation in the mouse heart caused by genetic deletion of malonyl CoA decarboxylase (MCD), SIRT5 demalonylase and desuccinylase, or SIRT3 deacetylase. In each case, elevated acylation is accompanied by marginal respiratory phenotypes. Of the >60 mitochondrial energy fluxes evaluated, the only outcome consistently observed across models is a ∼15% decrease in ATP synthase activity. In sum, the findings suggest that the vast majority of mitochondrial acyl PTMs occur as stochastic events that minimally affect mitochondrial bioenergetics.
This article was published in the following journal.
Name: Cell reports
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Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression.
Statistical models of the production, distribution, and consumption of goods and services, as well as of financial considerations. For the application of statistics to the testing and quantifying of economic theories MODELS, ECONOMETRIC is available.
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A set of models of how communication impacts and is impacted by subjective experience. Techniques are generated from these models by sequencing of various aspects of the models in order to change someone's internal representations. Neurolinguistic programming is concerned with the patterns or programming created by the interactions among the brain, language, and the body, that produce both effective and ineffective behavior.
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Cardiovascular disease (CVD)
Acute Coronary Syndromes (ACS) Blood Cardiovascular Dialysis Hypertension Stent Stroke Vascular Cardiovascular disease (CVD) includes all the diseases of the heart and circulation including coronary heart disease (angina...