Importance of mitochondrial quality control and its role in pathophysiology

Importance of mitochondrial quality control and its role in pathophysiology

Mitochondria are essential cell organelles that sustain life in multicellular organisms, from primitive organisms to highly differentiated mammals. They play critical roles in survival including energy production via oxidative phosphorylation, regulation of apoptosis, and calcium and reactive oxygen species signaling. Mitochondrial quality control mechanisms, including fission, fusion, and mitophagy, are thus critical for maintaining mitochondrial function, and their impairment causes many human diseases, including neurodegenerative diseases such as Alzheimer’s disease and Huntington’s disease, metabolic disorders, and cancer. Mitochondrial dynamics are maintained by balancing the functions of guanosine triphosphatase family proteins including fission proteins (dynamin-related protein 1, mitochondrial fission 1 protein) and fusion proteins (mitofusin-1/2, a dynamin-related protein). In particular, significant roles of Drp1 in mitochondrial structure, distribution, and pathophysiology have been demonstrated in many studies. Mitophagy, the process of selective mitochondrial degradation by autophagy, plays an important role in maintaining cellular homeostasis by eliminating dysfunctional mitochondria. This review addresses the importance of mitochondrial quality control and its role in human pathophysiology. We also introduce our recent studies on mitophagy.