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Gcn5l1 Promotes Enhanced Cardiac Fatty Acid Oxidation through Acetylation of Mitochondrial Proteins
Author(s) -
Thapa Dharendra,
Zhang Manling,
Guimarães Danielle A,
Stoner Michael W,
O'Doherty Robert M,
Shiva Sruti,
Scott Iain
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1080.3
Subject(s) - acetylation , beta oxidation , mitochondrion , biochemistry , lysine , fatty acid , enzyme , acetyltransferase , fatty acid metabolism , biology , chemistry , gene , amino acid
Lysine acetylation is a reversible post‐translational modification, and is particularly important in the regulation of mitochondrial metabolic enzymes. Acetylation uses acetyl‐CoA derived from fuel substrate metabolism as a co‐factor, which links nutritional inputs to metabolic activity. The objective of this study was to investigate the role of mitochondrial acetylation in the heart. Specifically, we assessed how food intake controls cardiac mitochondrial acetylation and affects mitochondrial metabolism. Western blots, immunoprecipitations, qPCR and mitochondrial bioenergetic assessments were performed to achieve these objectives. We found that there was a significant increase in cardiac mitochondrial protein acetylation in mice fed with a long‐term high fat diet, and that this change correlated with an increase in the abundance of the mitochondrial acetyltransferase‐related protein Gcn5l1. Further, we show that the acetylation status of two mitochondrial fatty acid oxidation enzymes was significantly upregulated in high fat diet mice, and that this was linked to increase in their enzymatic activity. Finally, we demonstrate that the acetylation of mitochondrial fatty acid oxidation proteins is decreased following Gcn5l1 knockdown, and that reduced acetylation leads to diminished fatty acid oxidation in cultured H9C2 cells. Based on our findings, we conclude that lysine acetylation promotes fatty acid oxidation in the heart, and that this modification is regulated in part by the activity of Gcn5l1. Support or Funding Information NHLBI K22HL116728