{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:43:45Z","timestamp":1780584225814,"version":"3.54.1"},"reference-count":95,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Center for Molecular Medicine and Genetics, Wayne State University School of Medicine"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 GM116807"],"award-info":[{"award-number":["R01 GM116807"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["2432\/23"],"award-info":[{"award-number":["2432\/23"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chief Scientist Office","award":["3-19245"],"award-info":[{"award-number":["3-19245"]}]},{"name":"Wayne State University Proteomics Core","award":["P30ES036084"],"award-info":[{"award-number":["P30ES036084"]}]},{"name":"Wayne State University Proteomics Core","award":["P30CA022453"],"award-info":[{"award-number":["P30CA022453"]}]},{"name":"Wayne State University Proteomics Core","award":["S10OD030484"],"award-info":[{"award-number":["S10OD030484"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Mitochondrial dysfunction contributes to diabetic cardiomyopathy, yet how genetic predisposition and diet interact to reshape cardiac metabolism in diabetic and prediabetic states remains unclear. The Cohen diabetic rat model, comprising diabetes-resistant (CDr) and diabetes-sensitive (CDs) strains, provides a unique platform to dissect this interplay. Here, we present an integrative global proteomic and bioenergetic characterization of cardiac tissue from CDr and CDs rats fed either a regular or a diabetogenic diet. Proteomic pathway mapping revealed downregulation of cytochrome c oxidase (CcO) subunits, strain-dependent rewiring of fatty-acid oxidation pathways, and CcO subunits switch from \u201cheart-type\u201d to \u201cliver-type\u201d isoforms in the sensitive strain. These changes were accompanied by impaired mitochondrial respiration, ATP depletion, and disruption of mitochondrial quality-control mechanisms, together with increased accumulation of tyrosine 304 phosphorylation of cytochrome c oxidase subunit I, indicative of inflammation-driven regulatory inhibition in a diet-specific manner. These findings establish an understanding of how genetic susceptibility and diet contribute to cardiac mitochondrial dysfunction in the Cohen diabetic rat model.<\/jats:p>","DOI":"10.3390\/antiox15020248","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T16:09:32Z","timestamp":1770998972000},"page":"248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrative Proteomic and Bioenergetic Profiling Reveals Diet- and Strain-Specific Mitochondrial Dysfunction in Cohen Diabetic Rat Hearts"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6229-623X","authenticated-orcid":false,"given":"Lauren","family":"Pavelich","sequence":"first","affiliation":[{"name":"Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA"},{"name":"Department of Biochemistry, Microbiology, and Immunology, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9644-3494","authenticated-orcid":false,"given":"Tasnim","family":"Arroum","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0872-4843","authenticated-orcid":false,"given":"Lucynda","family":"Pham","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8855-4291","authenticated-orcid":false,"given":"Dragana","family":"Komnenov","sequence":"additional","affiliation":[{"name":"Department of Physiology, Wayne State University, Detroit, MI 48201, USA"},{"name":"John D. 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