Biomolecules (Sep 2023)

Mitochondrial Calcium Overload Plays a Causal Role in Oxidative Stress in the Failing Heart

  • Haikel Dridi,
  • Gaetano Santulli,
  • Laith Bahlouli,
  • Marco C. Miotto,
  • Gunnar Weninger,
  • Andrew R. Marks

DOI
https://doi.org/10.3390/biom13091409
Journal volume & issue
Vol. 13, no. 9
p. 1409

Abstract

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Heart failure is a serious global health challenge, affecting more than 6.2 million people in the United States and is projected to reach over 8 million by 2030. Independent of etiology, failing hearts share common features, including defective calcium (Ca2+) handling, mitochondrial Ca2+ overload, and oxidative stress. In cardiomyocytes, Ca2+ not only regulates excitation–contraction coupling, but also mitochondrial metabolism and oxidative stress signaling, thereby controlling the function and actual destiny of the cell. Understanding the mechanisms of mitochondrial Ca2+ uptake and the molecular pathways involved in the regulation of increased mitochondrial Ca2+ influx is an ongoing challenge in order to identify novel therapeutic targets to alleviate the burden of heart failure. In this review, we discuss the mechanisms underlying altered mitochondrial Ca2+ handling in heart failure and the potential therapeutic strategies.

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