Regulatory role of mitochondria in oxidative stress and atherosclerosis

Mitochondrial physiology and biogenesis play a crucial role in the initiation and progression of cardiovascular disease following oxidative stress-induced damage such as atherosclerosis(AST).Dysfunctional mitochondria caused by an increase in mitochondrial reactive oxygen species(ROS)production,accumulation of mitochondrial DNA damage,and respiratory chain deficiency induces death of endothelial/smooth muscle cells and favors plaque formation/rupture via the regulation of mitochondrial biogenesis-related genes such as peroxisome proliferator-activated receptorγcoactivator(PGC-1),although more detailed mechanisms still need further study.Based on the effect of healthy mitochondria produced by mitochondrial biogenesis on decreasing ROS-mediated cell death and the recent finding that the regulation of PGC-1 involves mitochon- drial fusion-related protein(mitofusin),we thus infer the regulatory role of mitochondrial fusion/fission balance in AST pathophysiology.In this review,the first section discusses the possible association between AST-inducing factors and the molecular regulatory mechanisms of mitochondrial biogenesis and dynamics,and explains the role of mitochondria-dependent regulation in cell apoptosis during AST development. Furthermore,nitric oxide has the Janus-faced effect by protecting vascular damage caused by AST while being a reactive nitrogen species(RNS)which act together with ROS to damage cells.Therefore,in the second section we discuss mitochondrial ATP-sensitive K+ channels,which regulate mitochondrial ion transport to maintain mitochondrial physiology,involved in the regulation of ROS/RNS production and their influence on AST/cardiovascular diseases(CVD).Through this review,we can further appreciate the multi-regulatory functions of the mitochondria involved in AST development.The understanding of these related mechanisms will benefit drug development in treating AST/CVD through targeted biofunctions of mitochondria.