Mitochondrial redox status as a target for cardiovascular disease

Abstract

Mitochondria are major players in cellular energetics, oxidative stress and programmed cell death. Mitochondrial dynamics regulate and integrate these functions. Mitochondrial dysfunction is involved in cardiac hypertrophy, hypertension and myocardial ischemia/reperfusion injury. Reactive oxygen species generation is modulated by the fusion-fission pathway as well as key proteins such as sirtuins that act as metabolic sensors of cellular energetics. Mitochondrial redox status has thus become a good target for therapy against cardiovascular diseases. Recently, there is an influx of studies garnered towards assessing the beneficial effects of mitochondrial targeted antioxidants, drugs modulating the fusion-fission proteins, sirtuins, and other mitochondrial processes as potential cardio-protecting agents.

Figure 1. Mitochondrial dynamics within a cardiomyocyte

A. Diagram of cardiomyocyte mitochondrial architecture within the myofibrils. a. capillary and red blood cell, b. lysosome, c. closely packed mitochondria between myofibril layers, d. Z disks, A band, I band, and M Line of myofibrils, c. mitochondria undergoing autophagy (mitophagy). B. Fusion and fission targets and their respective therapeutic drugs. C. Diagram of reactive oxygen production and scavenging in relation to mitochondrial fusion and fission proteins (DRP1, Fis1, Mfn1, Mfn2 OPA1) and Sirt regulators of apoptosis, ROS regulation and fusion and fission.