PINK1 and Parkin: team players in stress-induced mitophagy
Verian Bader, Konstanze F. Winklhofer
Abstract
Mitochondria are highly vulnerable organelles based on their complex biogenesis, entailing dependence on nuclear gene expression and efficient import strategies. They are implicated in a wide spectrum of vital cellular functions, including oxidative phosphorylation, iron-sulfur cluster synthesis, regulation of calcium homeostasis, and apoptosis. Moreover, damaged mitochondria can release mitochondrial components, such as mtDNA or cardiolipin, which are sensed as danger-associated molecular patterns and trigger innate immune signaling. Thus, dysfunctional mitochondria pose a thread not only to the cellular but also to the organismal integrity. The elimination of dysfunctional and damaged mitochondria by selective autophagy, called mitophagy, is a major mechanism of mitochondrial quality control. Certain types of stress-induced mitophagy are regulated by the mitochondrial kinase PINK1 and the E3 ubiquitin ligase Parkin, which are both linked to autosomal recessive Parkinson's disease.