Mitochondrial Dysfunction in Chronic Respiratory Diseases: Implications for the Pathogenesis and Potential Therapeutics

Figure 1

Normal mitochondria are sustained by stabilization of MMP, balance of mitochondrial calcium, integrity of mtDNA, and timely clearance of damaged mitochondria via mitophagy. The electron flows from complex I to complex IV, which creates a direct electric current that terminates in subunit II of complex IV for MMP. This is accompanied by the synthesis of ATP. Mitochondria are closely linked to the ER. They intimately and dynamically communicate, thereby forming very dynamic platforms termed MAM. The delivery of ER-mitochondria calcium mainly depends on IP3 receptors (IP3R) and voltage-dependent anion channel (VDAC). Mitochondrial calcium uptake is mediated by the MCU complex, while calcium release depends on mHCX and NCLX systems. Mitochondrion harbors its own DNA, which encodes many critical proteins for the assembly and activity of mitochondrial respiratory complexes. Mitochondria are dynamic through fission and fusion. Mitophagy is a selective and adaptive response and plays a critical role in surveilling mitochondrial quality and preventing accumulation of dysfunctional mitochondria.