{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:54:26Z","timestamp":1761598466685,"version":"build-2065373602"},"reference-count":75,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Detroit Cardiovascular Training Program: ARK","award":["NIH 2 T32 HL120822"],"award-info":[{"award-number":["NIH 2 T32 HL120822"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Disruption of mitochondrial structure\/function is well-recognized to be a determinant of cell death in cardiomyocytes subjected to lethal episodes of ischemia-reperfusion (IR). However, the precise mitochondrial event(s) that precipitate lethal IR injury remain incompletely resolved. Using the in vitro HL-1 cardiomyocyte model, our aims were to establish whether: (1) proteolytic processing of optic atrophy protein-1 (OPA1), the inner mitochondrial membrane protein responsible for maintaining cristae junction integrity, plays a causal, mechanistic role in determining cardiomyocyte fate in cells subjected to lethal IR injury; and (2) preservation of OPA1 may contribute to the well-documented cardioprotection achieved with ischemic preconditioning (IPC) and remote ischemic conditioning. We report that HL-1 cells subjected to 2.5 h of simulated ischemia displayed increased activity of OMA1 (the metalloprotease responsible for proteolytic processing of OPA1) during the initial 45 min following reoxygenation. This was accompanied by processing of mitochondrial OPA1 (i.e., cleavage to yield short-OPA1 peptides) and release of short-OPA1 into the cytosol. However, siRNA-mediated knockdown of OPA1 content did not exacerbate lethal IR injury, and did not attenuate the cardioprotection seen with IPC and a remote preconditioning stimulus, achieved by transfer of \u2018reperfusate\u2019 medium (TRM-IPC) in this cell culture model. Taken together, our results do not support the concept that maintenance of OPA1 integrity plays a mechanistic role in determining cell fate in the HL-1 cardiomyocyte model of lethal IR injury, or that preservation of OPA1 underlies the cardioprotection seen with ischemic conditioning.<\/jats:p>","DOI":"10.3390\/cells11193083","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T01:52:21Z","timestamp":1665193941000},"page":"3083","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Does Disruption of Optic Atrophy-1 (OPA1) Contribute to Cell Death in HL-1 Cardiomyocytes Subjected to Lethal Ischemia-Reperfusion Injury?"],"prefix":"10.3390","volume":"11","author":[{"given":"Andrew R.","family":"Kulek","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vishnu V. R.","family":"Undyala","sequence":"additional","affiliation":[{"name":"Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA"},{"name":"Clinical Research Institute, Children\u2019s Hospital of Michigan & Department of Pediatrics, Central Michigan University, Detroit, MI 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony R.","family":"Anzell","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarita","family":"Raghunayakula","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1715-6402","authenticated-orcid":false,"given":"Lee Ann","family":"MacMillan-Crow","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas H.","family":"Sanderson","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9602-6349","authenticated-orcid":false,"given":"Karin","family":"Przyklenk","sequence":"additional","affiliation":[{"name":"Clinical Research Institute, Children\u2019s Hospital of Michigan & Department of Pediatrics, Central Michigan University, Detroit, MI 48201, USA"},{"name":"Departments of Physiology and Emergency Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1007\/s00395-013-0392-7","article-title":"Redox balance and cardioprotection","volume":"108","author":"Tullio","year":"2013","journal-title":"Basic Res. 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