Molecular mechanisms of PINK1-related neurodegeneration

PINK1 is a mitochondrially targeted kinase that has been linked to a rare monogenic form of Parkinson's disease (PD), a common neurodegenerative disease characterized by the degeneration of selected dopaminergic neurons. Intensive research using many model systems has clearly established a fundamental role for PINK1 in preventing mitochondrial dysfunction-a key mechanism long thought to play a central role in PD pathogenesis. Current hypotheses propose PINK1's important functions involve mitophagy, mitochondrial calcium buffering, and mitochondrial quality control. Furthermore, recent findings have revealed that PINK1's functions are likely regulated by a complex mechanism that includes regulated mitochondrial import and intramembrane proteolysis to influence its sub cellular and sub mitochondrial distribution. This review aims to summarize and evaluate recent findings, with particular emphasis on PINK1 localization, cleavage, and function in mitochondrial homeostasis.