Mitochondrial quality control in the myocardium: cooperation between protein degradation and mitophagy

J Mol Cell Cardiol. 2014 Oct;75:122-30. doi: 10.1016/j.yjmcc.2014.07.013. Epub 2014 Jul 30.


Mitochondria are critical for cardiomyocyte survival and maintenance of normal cardiac function. However, changes in the extra- or intracellular environments during stress can cause excessive damage to mitochondria and lead to activation of cell death. In fact, there is evidence that mitochondrial dysfunction is an important contributor to both development of heart failure and the aging process. To counteract the adverse effects resulting from mitochondrial damage, cells have evolved mitochondrial quality control pathways that act at both the protein and organelle levels. Quality control of proteins in the outer mitochondrial membrane is monitored by the ubiquitin-protease system, whereas chaperones and proteases act in the various compartments of the mitochondria. When the damage is too excessive and the degradation machinery is overwhelmed, the entire mitochondrion is eliminated by an autophagosome. Together, these pathways ensure that myocytes maintain a functional network of mitochondria which provides ATP for contraction. Unfortunately, chronic stress and aging can negatively affect proteins that are involved in the mitochondrial quality control pathways which leads to accumulation of dysfunctional mitochondria and loss of myocytes. In this review, we provide an overview of the proteins and pathways that regulate mitochondrial quality control in the cell with an emphasis on pathways involved in maintaining protein and organelle homeostasis. We also delve into the effects of reduced mitochondrial quality control on aging and cardiovascular disease.

Keywords: Aging; Autophagy; Mitochondria; Mitophagy; Parkin; Proteases.

Publication types

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

MeSH terms

  • Animals
  • Disease
  • Humans
  • Mitochondria, Heart / metabolism*
  • Mitochondrial Proteins / metabolism
  • Mitophagy*
  • Myocardium / metabolism*
  • Proteolysis*


  • Mitochondrial Proteins