Mitochondrial dysfunction in heart failure and its therapeutic implications

Abstract

The ATP consumption in heart is very intensive to support muscle contraction and relaxation. Mitochondrion is the power plant of the cell. Mitochondrial dysfunction has long been believed as the primary mechanism responsible for the inability of energy generation and utilization in heart failure. In addition, emerging evidence has demonstrated that mitochondrial dysfunction also contributes to calcium dysregulation, oxidative stress, proteotoxic insults and cardiomyocyte death. These elements interact with each other to form a vicious circle in failing heart. The role of mitochondrial dysfunction in the pathogenesis of heart failure has attracted increasing attention. The complex signaling of mitochondrial quality control provides multiple targets for maintaining mitochondrial function. Design of therapeutic strategies targeting mitochondrial dysfunction holds promise for the prevention and treatment of heart failure.

Keywords: calcium; fusion and fission; heart failure; mitochondria; mitophagy; reactive oxygen species.

FIGURE 1

Mitochondrial quality control and mitochondrial dysfunction in the pathophysiology of heart failure. Mitochondrial quality control mainly includes UPS/UPRmt, mitochondrial fusion and fission, and mitophagy to ensure the number, morphology and function of mitochondria. Mitochondrial dysfunction leads to energy metabolism disturbance, Ca²⁺ dysregulation, oxidative stress, proteotoxic insults, and cardiomyocyte death in the heart, and contributes to the progression of heart failure. mtROS, mitochondrial reactive oxygen species; UPS, ubiquitin-proteasome system; UPRmt, mitochondrial unfolded protein response.