{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:43:42Z","timestamp":1789526622581,"version":"build-2803163510"},"reference-count":88,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"crossref","award":["964800"],"award-info":[{"award-number":["964800"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007465","name":"UiT-The Arctic University of Norway","doi-asserted-by":"crossref","award":["2061348"],"award-info":[{"award-number":["2061348"]}],"id":[{"id":"10.13039\/100007465","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The paradoxical exacerbation of cellular injury and death during reperfusion remains a problem in the treatment of myocardial infarction. Mitochondrial dysfunction plays a key role in the pathogenesis of myocardial ischemia and reperfusion injury. Dysfunctional mitochondria can be removed by mitophagy, culminating in their degradation within acidic lysosomes. Mitophagy is pivotal in maintaining cardiac homeostasis and emerges as a potential therapeutic target. Here, we employed beating human engineered heart tissue (EHT) to assess mitochondrial dysfunction and mitophagy during ischemia and reperfusion simulation. Our data indicate adverse ultrastructural changes in mitochondrial morphology and impairment of mitochondrial respiration. Furthermore, our pH-sensitive mitophagy reporter EHTs, generated by a CRISPR\/Cas9 endogenous knock-in strategy, revealed induced mitophagy flux in EHTs after ischemia and reperfusion simulation. The induced flux required the activity of the protein kinase ULK1, a member of the core autophagy machinery. Our results demonstrate the applicability of the reporter EHTs for mitophagy assessment in a clinically relevant setting. Deciphering mitophagy in the human heart will facilitate development of novel therapeutic strategies.<\/jats:p>","DOI":"10.1242\/jcs.263408","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T06:28:36Z","timestamp":1738823316000},"source":"Crossref","is-referenced-by-count":12,"title":["Mitophagy is induced in human engineered heart tissue after simulated ischemia and reperfusion"],"prefix":"10.1242","volume":"138","author":[{"given":"Mireia","family":"N\u00e0ger","sequence":"first","affiliation":[{"name":"University Hospital of North Norway 1 Division of Cardiothoracic and Respiratory Medicine , , 9019 Troms\u00f8 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth B.","family":"Larsen","sequence":"additional","affiliation":[{"name":"UiT-The Arctic University of Norway 2 Department of Clinical Medicine , , 9019 Troms\u00f8 ,","place":["Norway"]},{"name":"UiT-The Arctic University of Norway 3 Department of Medical Biology , , 9019 Troms\u00f8 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zambarlal","family":"Bhujabal","sequence":"additional","affiliation":[{"name":"UiT-The Arctic University of Norway 2 Department of Clinical Medicine , , 9019 Troms\u00f8 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine B.","family":"Kalstad","sequence":"additional","affiliation":[{"name":"UiT-The Arctic University of Norway 2 Department of Clinical Medicine , , 9019 Troms\u00f8 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"R\u00f6ssinger","sequence":"additional","affiliation":[{"name":"University Medical Center Hamburg Eppendorf 4 Department of Experimental Pharmacology and Toxicology , , ,","place":["Germany"]},{"name":"20251 Hamburg 4 Department of Experimental Pharmacology and Toxicology , , ,","place":["Germany"]},{"name":"DZHK (German Center for Cardiovascular Research), partner site Hamburg\/Kiel\/L\u00fcbeck 5 , 20251 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Truls","family":"Myrmel","sequence":"additional","affiliation":[{"name":"University Hospital of North Norway 1 Division of Cardiothoracic and Respiratory Medicine , , 9019 Troms\u00f8 ,","place":["Norway"]},{"name":"UiT-The Arctic University of Norway 2 Department of Clinical Medicine , , 9019 Troms\u00f8 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Weinberger","sequence":"additional","affiliation":[{"name":"University Medical Center Hamburg Eppendorf 4 Department of Experimental Pharmacology and Toxicology , , ,","place":["Germany"]},{"name":"20251 Hamburg 4 Department of Experimental Pharmacology and Toxicology , , ,","place":["Germany"]},{"name":"DZHK (German Center for Cardiovascular Research), partner site Hamburg\/Kiel\/L\u00fcbeck 5 , 20251 Hamburg ,","place":["Germany"]},{"name":"Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) 6 , 28029 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1080-3619","authenticated-orcid":false,"given":"Asa B.","family":"Birgisdottir","sequence":"additional","affiliation":[{"name":"University Hospital of North Norway 1 Division of Cardiothoracic and Respiratory Medicine , , 9019 Troms\u00f8 ,","place":["Norway"]},{"name":"UiT-The Arctic University of Norway 2 Department of Clinical Medicine , , 9019 Troms\u00f8 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"2025031904495919700_JCS263408C1","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1093\/eurheartj\/ehae782","article-title":"Enhanced Parkin-mediated mitophagy mitigates adverse left ventricular remodelling after myocardial infarction: role of PR-364","volume":"46","author":"Ai","year":"2025","journal-title":"Eur. 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