Research Projects

Mitophagy is crucial for maintaining mitochondria and cellular homeostasis, and impaired mitophagy can lead to neurological disorders like Parkinson's disease, dementia, Alzheimer's, and cardiomyopathies. PINK1, a 64 kDa ser/Thr kinase, is a potential marker for mitophagy. In healthy mitochondria, PINK1 precursor is imported to the matrix, MPP cleaves off the MTs, and PARL, a protease, cleaves PINK1 and generates a less stable 52 kDa fragment. However, PINK1 import is stalled in damaged mitochondria due to membrane potential depletion, resulting in the accumulation and stabilization of unprocessed PINK1 on the outer mitochondrial membrane. stabilization of the entire PINK1 is essential for parkin-mediated clearance of damaged mitochondria. MIA40, a component of the intermembrane space protein import machinery of mitochondria, is involved in respiratory chain activities, regulation of ROs, and Fe-s cluster export. PINK1 has a characteristic twin Cx3C and Cx9C motif, and interaction with MIA40 and overexpression reduce CCCP/PINK1 mediated mitophagy. The researchers aim to decipher the mechanism of PINK1 protein import and stabilization and the role of MIA40 in this process. They plan to use yeast as a surrogate system for in vitro import kinetics to study MIA40's role in importing PINK1 and the topology of PINK1 before and after stabilization. Additionally, they plan to study glutathionylation of MIA40 in mitophagy regulation mediated by the PINK1 and Parkin pathway.