Mitochondrial calcium handling and heart disease in diabetes mellitus

Biochim Biophys Acta Mol Basis Dis. 2021 Jan 1;1867(1):165984. doi: 10.1016/j.bbadis.2020.165984. Epub 2020 Sep 28.

Abstract

Diabetes mellitus-induced heart disease, including diabetic cardiomyopathy, is an important medical problem and is difficult to treat. Diabetes mellitus increases the risk for heart failure and decreases cardiac myocyte function, which are linked to changes in cardiac mitochondrial energy metabolism. The free mitochondrial calcium concentration ([Ca2+]m) is fundamental in activating the mitochondrial respiratory chain complexes and ATP production and is also known to regulate the activity of key mitochondrial dehydrogenases. The mitochondrial calcium uniporter complex (MCUC) plays a major role in mediating mitochondrial Ca2+ import, and its expression and function therefore may have a marked impact on cardiac myocyte metabolism and function. Here, we summarize the pathophysiological role of [Ca2+]m handling and MCUC in the diabetic heart. In addition, we evaluate potential therapeutic targets, directed to the machinery that regulates mitochondrial calcium handling, to alleviate diabetes-related cardiac disease.

Keywords: Cardiac myocytes; Diabetic cardiomyopathy; Mitochondrial calcium; Mitochondrial calcium uptake and release; Therapeutic target.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Calcium Channels / metabolism*
  • Calcium Signaling*
  • Diabetic Cardiomyopathies / metabolism*
  • Diabetic Cardiomyopathies / pathology
  • Humans
  • Mitochondria, Heart / metabolism*
  • Mitochondria, Heart / pathology
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology

Substances

  • Calcium Channels
  • mitochondrial calcium uniporter