PINK1 and Parkin: team players in stress-induced mitophagy

Abstract

AbstractMitochondria 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.