A naturally occurring mutation in ATP synthase subunit c is associated with increased damage following hypoxia/reoxygenation in STEMI patients

• Main Authors: Giampaolo Morciano, Gaia Pedriali, Massimo Bonora, Rita Pavasini, Elisa Mikus, Simone Calvi, Matteo Bovolenta, Magdalena Lebiedzinska-Arciszewska, Mirko Pinotti, Alberto Albertini, Mariusz R. Wieckowski, Carlotta Giorgi, Roberto Ferrari, Lorenzo Galluzzi, Gianluca Campo, Paolo Pinton
• Format: Article
• Language: English
• Published: Elsevier 2021-04-01
• Series: Cell Reports
• Subjects: cardiovascular diseases; PTP; mitochondria; reperfusion injury; glycine-rich domain; STEMI patients
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124721002977
• ISSN: 2211-1247

Summary: Preclinical models of ischemia/reperfusion injury (RI) demonstrate the deleterious effects of permeability transition pore complex (PTPC) opening in the first minutes upon revascularization of the occluded vessel. The ATP synthase c subunit (Csub) influences PTPC activity in cells, thus impacting tissue injury. A conserved glycine-rich domain in Csub is classified as critical because, when mutated, it modifies ATP synthase properties, protein interaction with the mitochondrial calcium (Ca2+) uniporter complex, and the conductance of the PTPC. Here, we document the role of a naturally occurring mutation in the Csub-encoding ATP5G1 gene at the G87 position found in two ST-segment elevation myocardial infarction (STEMI) patients and how PTPC opening is related to RI in patients affected by the same disease. We report a link between the expression of ATP5G1G87E and the response to hypoxia/reoxygenation of human cardiomyocytes, which worsen when compared to those expressing the wild-type protein, and a positive correlation between PTPC and RI.