Wang Yuqing, Serricchio Mauro, Jauregui Miluska, Shanbhag Riya, Stoltz Tasha, Di Paolo Caitlin T, Kim Peter K, McQuibban G Angus (2015), Deubiquitinating enzymes regulate PARK2-mediated mitophagy., in
Autophagy, 11(4), 595-606.
Sing Anson, Tsatskis Yonit, Fabian Lacramioara, Hester Ian, Rosenfeld Robyn, Serricchio Mauro, Yau Norman, Bietenhader Maïlis, Shanbhag Riya, Jurisicova Andrea, Brill Julie A, McQuibban G Angus, McNeill Helen (2014), The atypical cadherin fat directly regulates mitochondrial function and metabolic state., in
Cell, 158(6), 1293-308.
Once considered just the powerhouse of the cell, mitochondria are central players in several signaling pathways, and are important mediators of life and death decisions in the cell. Dysfunction in maintaining a healthy mitochondrial network has been linked to many neurodegenerative diseases like Parkinson’s disease. Mitochondria are extremely dynamic, constantly undergoing membrane fusion and fission reactions. It has been proposed that these fusion-fission pathways serve as a mechanism to maintain a healthy mitochondrial network. Damaged mitochondria are degraded by a mechanism called mitophagy. Ubiquitylation of mitochondrial proteins by E3 ligases targets the proteins for degradation by the ubiquitin-proteasome system and triggers mitophagy. As ubiquitylation is a reversible modification, my global hypothesis is that de-ubiquitylation will be an important feature to regulate the cell’s mitophagic response upon mitochondrial damage. 6 human mitochondrial deubiquitin-proteases have been identified in the host laboratory. We propose to characterize the molecular mechanisms of the 6 uncharacterized proteases. By using live cell imaging, Western blot analysis, cell fractionation experiments, RNAi knock-down or overexpression experiments we plan to address the following points:1) Identify which of the 6 mitochondrial deubiquitin proteases directly affects mitophagy.2) Identify at which stage of mitophagy the deubiquitin protease is working.3) Identify the protein targets of the deubiquitin proteases.