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

Overview

abstract

  • 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.

publication date

  • April 13, 2021

Research

keywords

  • Hypoxia
  • Mitochondria
  • Mitochondrial Permeability Transition Pore
  • Mitochondrial Proton-Translocating ATPases
  • Myocytes, Cardiac
  • ST Elevation Myocardial Infarction

Identity

Scopus Document Identifier

  • 85104069595

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2021.108983

PubMed ID

  • 33852870

Additional Document Info

volume

  • 35

issue

  • 2