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

Figure 2

Potential mechanisms to direct deubiquitination at the mitochondria. The diagram illustrates the multiple ways in which DUBs may function at the mitochondria. (a) DUBs such as USP30 can reside in the OMM, in an orientation that provides access to ubiquitin-modified OMM proteins. (b) Substrate-specific DUBs, like USP9x and ataxin-3, might be directly recruited to the mitochondria by their substrates, Mcl1 and Parkin, respectively. (c) It is also possible that DUBs are affixed at the membrane through protein interactions with nonsubstrate proteins at the OMM. This arrangement can bring deubiquitinases in close proximity to their substrates. Although DUBs that use such a mechanism have not yet been identified, the finding that most DUBs contain multiple protein-protein interaction domains lends support to this view. (d) Certain cellular conditions, such as ROS-induced stress, may recruit cytoplasmic DUBs to the mitochondria to counteract the damage.