Acetylation of mitochondrial proteins by GCN5L1 promotes enhanced fatty acid oxidation in the heart

American Journal of Physiology. Heart and Circulatory Physiology
Dharendra ThapaIain Scott

Abstract

Lysine acetylation is a reversible posttranslational modification and is particularly important in the regulation of mitochondrial metabolic enzymes. Acetylation uses acetyl-CoA derived from fuel metabolism as a cofactor, thereby linking nutrition to metabolic activity. In the present study, we investigated how mitochondrial acetylation status in the heart is controlled by food intake and how these changes affect mitochondrial metabolism. We found that there was a significant increase in cardiac mitochondrial protein acetylation in mice fed a long-term high-fat diet and that this change correlated with an increase in the abundance of the mitochondrial acetyltransferase-related protein GCN5L1. We showed that the acetylation status of several mitochondrial fatty acid oxidation enzymes (long-chain acyl-CoA dehydrogenase, short-chain acyl-CoA dehydrogenase, and hydroxyacyl-CoA dehydrogenase) and a pyruvate oxidation enzyme (pyruvate dehydrogenase) was significantly upregulated in high-fat diet-fed mice and that the increase in long-chain and short-chain acyl-CoA dehydrogenase acetylation correlated with increased enzymatic activity. Finally, we demonstrated that the acetylation of mitochondrial fatty acid oxidation proteins was dec...Continue Reading

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Citations

Aug 21, 2018·The Journal of Clinical Investigation·Bo Zhou, Rong Tian
Jun 25, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Rami Al Batran, John R Ussher
Aug 23, 2018·Frontiers in Physiology·Rebecca M Parodi-RullánSabzali Javadov
Nov 25, 2019·Journal of Physiology and Biochemistry·Tingting LvQiang Wan
Jul 22, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Merry L LindseyDouglas Curran-Everett
Jun 21, 2019·The Biochemical Journal·Qutuba G KarwiGary D Lopaschuk
Jan 15, 2021·Clinical Science·Md Ezazul HaqueDong-Kug Choi
Feb 19, 2019·Journal of Molecular and Cellular Cardiology·Janet R ManningIain Scott
Feb 27, 2018·Trends in Cell Biology·Iain ScottMichael N Sack
May 1, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Amanda A GreenwellJohn R Ussher
Aug 20, 2021·Frontiers in Cardiovascular Medicine·Ezra B Ketema, Gary D Lopaschuk

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Methods Mentioned

BETA
acetylation
coimmunoprecipitation
gene knockdown
pulldown

Software Mentioned

ImageJ

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