The Emerging Role of Proteolysis in Mitochondrial Quality Control and the Etiology of Parkinson’s Disease

Figure 6

Interdependence of mitochondrial functions. Mitochondria generate ATP energy for the cell with the help of the electron transport chain. ATP fuels many cellular processes including protein degradation by the 26S proteasome. Hence, the process of oxidative phosphorylation (OXPHOS) influences the function of mitochondrial quality control systems. In the reverse direction, components of the quality control pathways can influence OXPHOS. Parkin mutants and defects in PINK1 have been shown to reduce mitochondrial respiration; PINK1 defects impair complex I functionality. In addition, mammalian studies with ataxin-3 mutants showed reduced complex II activity. Mitochondrial dysfunction can trigger apoptosis. Failures within the quality control system, coupled with an increase in ROS, can lead to the release of proapoptotic proteins. For example, if sufficient amounts of Mcl1 are not maintained due to unrestrained proteasomal degradation, Bak can facilitate the release of AIF/cytC and induce apoptosis. Hence, it is important for the quality control mechanisms to function properly in order to prevent unsolicited downstream effects. Overall, the mitochondrial network has to maintain a refined balance between all of these processes and direct effective metabolic outputs depending on the environmental and/or developmental context.