{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:11:42Z","timestamp":1790255502596,"version":"4.1.0"},"reference-count":68,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"NIH\/NHLBI K99\/R00","doi-asserted-by":"publisher","award":["HL 146905"],"award-info":[{"award-number":["HL 146905"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH\/NHLBI R01","award":["HL 168290"],"award-info":[{"award-number":["HL 168290"]}]},{"DOI":"10.13039\/100000066","name":"NIH\/NIEHS R01","doi-asserted-by":"publisher","award":["ES 034628"],"award-info":[{"award-number":["ES 034628"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Community Foundation for the Ohio Valley Whipkey Trust"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Precise control of mitochondrial electron transport is essential to maintain mitochondrial coupling and efficiency in ATP production. Furthermore, disruptions to ETC complex function can drive increased oxidant production, resulting in oxidative damage to the mitochondrion and bioenergetic inefficiency. This is highly relevant in the aging heart, as increased cardiac oxidative stress and mitochondrial dysfunction are hallmarks of age-related cardiovascular disease. Lysine acetylation has recently been characterized as a novel regulator of mitochondrial metabolic and bioenergetic function in the aging heart. In the present study, we investigated how lysine acetylation regulates oxidant production and redox milieu through mitochondrial acetyltransferase GCN5L1. Using a cardiac-specific GCN5L1 knockout mouse model, we observed that age-associated lipid peroxidation and semiquinone radicals were decreased with GCN5L1 KO. RNA sequencing analysis identified mitochondrial bioenergetic and respiratory pathways revolving around the respiratory chain to be enriched in the old KO group. Further, we showed the old KO group to exhibit reduced acetylation of ETC complex and antioxidant proteins, improved ETC complex and antioxidant protein activity. Overall, GCN5L1 regulates redox homeostasis in the aged heart by regulating mitochondrial ETC complex activity, oxidative stress, and mitochondrial bioenergetics. These findings identify GCN5L1 and acetylation as potential therapeutic targets in aging and age-related diseases.<\/jats:p>","DOI":"10.3390\/antiox15040481","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T10:19:14Z","timestamp":1776075554000},"page":"481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["GCN5L1-Mediated Lysine Acetylation Regulates Mitochondrial Bioenergetics and Redox Homeostasis in the Aged Heart"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8281-0783","authenticated-orcid":false,"given":"Jackson E.","family":"Stewart","sequence":"first","affiliation":[{"name":"Division of Exercise Physiology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Mitochondria, Metabolism & Bioenergetics Working Group, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahatul","family":"Islam","sequence":"additional","affiliation":[{"name":"Division of Exercise Physiology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Mitochondria, Metabolism & Bioenergetics Working Group, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9633-7596","authenticated-orcid":false,"given":"Ethan","family":"Meadows","sequence":"additional","affiliation":[{"name":"Mitochondria, Metabolism & Bioenergetics Working Group, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4917-5525","authenticated-orcid":false,"given":"Joshua P.","family":"Mogus","sequence":"additional","affiliation":[{"name":"Mitochondria, Metabolism & Bioenergetics Working Group, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Department of Physiology, Pharmacology & Toxicology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9751-538X","authenticated-orcid":false,"given":"Murugesan","family":"Velayutham","sequence":"additional","affiliation":[{"name":"In Vivo Multifunctional Magnetic Resonance Center, Department of Biochemistry and Molecular Medicine, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery V.","family":"Khramtsov","sequence":"additional","affiliation":[{"name":"In Vivo Multifunctional Magnetic Resonance Center, Department of Biochemistry and Molecular Medicine, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Scott","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Hollander","sequence":"additional","affiliation":[{"name":"Mitochondria, Metabolism & Bioenergetics Working Group, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Department of Physiology, Pharmacology & Toxicology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharendra","family":"Thapa","sequence":"additional","affiliation":[{"name":"Division of Exercise Physiology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Mitochondria, Metabolism & Bioenergetics Working Group, School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1161\/CIRCRESAHA.111.246876","article-title":"The intersection between aging and cardiovascular disease","volume":"110","author":"North","year":"2012","journal-title":"Circ. 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