{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:14:38Z","timestamp":1790720078544,"version":"4.1.0"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,7,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Desmin filament proteins interlink the contractile myofibrillar apparatus with mitochondria, nuclei and the sarcolemma. Mutations in the human desmin gene cause cardiac disease, remodeling, and heart failure but the pathophysiological mechanisms remain unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Cardiomyocyte\u2010specific overexpression of mutated desmin (a 7 amino acid deletion R172\u2010E178, D7\u2010Des Tg) causes accumulations of electron\u2010dense aggregates and myofibrillar degeneration associated with cardiac dysfunction. Though extensive studies demonstrated that these altered ultrastructural changes cause impairment of cardiac contractility, the molecular mechanism of cardiomyocyte death remains elusive. In the present study, we report that the D7\u2010Des Tg mouse hearts undergo aberrant mitochondrial fission associated with increased expression of mitochondrial fission regulatory proteins. Mitochondria isolated from D7\u2010Des Tg hearts showed decreased mitochondrial respiration and increased apoptotic cell death. Overexpression of mutant desmin by adenoviral infection in cultured cardiomyocytes led to increased mitochondrial fission, inhibition of mitochondrial respiration, and activation of cellular toxicity. Inhibition of mitochondrial fission by mitochondrial division inhibitor mdivi\u20101 significantly improved mitochondrial respiration and inhibited cellular toxicity associated with D7\u2010Des overexpression in cardiomyocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Aberrant mitochondrial fission results in mitochondrial respiratory defects and apoptotic cell death in D7\u2010Des Tg hearts. Inhibition of aberrant mitochondrial fission using mitochondrial division inhibitor significantly preserved mitochondrial function and decreased apoptotic cell death. Taken together, our study shows that maladaptive aberrant mitochondrial fission causes desminopathy\u2010associated cellular dysfunction.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.118.009289","type":"journal-article","created":{"date-parts":[[2018,7,9]],"date-time":"2018-07-09T09:15:13Z","timestamp":1531127713000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["Aberrant Mitochondrial Fission Is Maladaptive in Desmin Mutation\u2013Induced Cardiac Proteotoxicity"],"prefix":"10.1161","volume":"7","author":[{"given":"Shafiul","family":"Alam","sequence":"first","affiliation":[{"name":"Department of Pathology and Translational Pathobiology Louisiana State University Health Sciences Center Shreveport LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chowdhury S.","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Department of Pathology and Translational Pathobiology Louisiana State University Health Sciences Center Shreveport LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Aishwarya","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center Shreveport LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumitra","family":"Miriyala","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy Louisiana State University Health Sciences Center Shreveport LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manikandan","family":"Panchatcharam","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy Louisiana State University Health Sciences Center Shreveport LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonette M.","family":"Peretik","sequence":"additional","affiliation":[{"name":"Department of Pathology and Translational Pathobiology Louisiana State University Health Sciences Center Shreveport LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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