FIGURE 2.

Different pathomechanisms converge on mitochondria in Parkinson’s disease. (A) PINK1 and parkin mediate mitochondrial quality control processes such as mitophagy. PINK1 is also required for phosphorylation of Ndufa10 to facilitate the reduction of ubiquinone by complex I. (B) Mutations in LRRK2 block mitophagy by preventing the degradation of Miro or by trapping Rab10 whose interaction with OPTN is pivotal for autophagy/mitophagy. (C) DJ-1 scavenges ROS through sequential oxidation at Cys106. The oxidized DJ-1 acts as a chaperone to facilitate the assembly and activities of cI, cIV, and cV. (D) Accumulation of GlcCer and other lipids in GCase mutants impairs lysosomal functions. Mutations in GCase reduces the expression of NMNAT2, resulting in a significant reduction of NAD + /NADH. (E) α-Syn monomers or oligomers interrupt the activities of cI and cV. The fibrilized α-Syn triggers Lewy body formation which sequestrates abundant mitochondria. (F) Deficits in iPLA2-β cause lipid imbalance that may interrupt ETC functions. (G) UQCRC1 is critical in cIII assembly and functions, and also prevents cyt c release. (H) CHCHD2 is a chaperone of cIV, activates COX4I2 and its own expression, complexes with MICS to prevent cyt c release, and regulates the cristae structure by stabilizing OPA1 and MICOS complex.