2026-06-14T03:31:32Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/268312025-12-18T13:01:55Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587
Repisalud
author
Nàger, Mireia
author
Larsen, Kenneth B
author
Bhujabal, Zambarlal
author
Kalstad, Trine B
author
Rössinger, Judith
author
Myrmel, Truls
author
Weinberger, Florian
author
Birgisdottir, Asa B
funder
Unión Europea. Comisión Europea. H2020
2025-07-16T14:15:20Z
2025-07-16T14:15:20Z
2025-05-01
J Cell Sci. 2025 May 1;138(9):jcs263408.
Journal of Cell Science
39912384
https://hdl.handle.net/20.500.12105/26831
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.
eng
Engineered heart tissue
Ischemia–reperfusion
Mitochondria
Mitophagy
hiPSC
Mitophagy is induced in human engineered heart tissue after simulated ischemia and reperfusion.
research article
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URL
https://repisalud.isciii.es/bitstreams/ac85783c-4296-48f0-ac03-48dca23a78d8/download
File
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0b71504abeb63d5d40cc04d4b484d44d
13114844
application/pdf
Mitophagy is induced_J Cell Sci_2025.pdf