The role of PINK1–Parkin in mitochondrial quality control

Mitophagy mediated by the recessive Parkinson’s disease genes PINK1 and Parkin responds to mitochondrial damage to preserve mitochondrial function. In the pathway, PINK1 is the damage sensor, probing the integrity of the mitochondrial import pathway, and activating Parkin when import is blocked. Parkin is the effector, selectively marking damaged mitochondria with ubiquitin for mitophagy and other quality-control processes. This selective mitochondrial quality-control pathway may be especially critical for dopamine neurons affected in Parkinson’s disease, in which the mitochondrial network is widely distributed throughout a highly branched axonal arbor. Here we review the current understanding of the role of PINK1–Parkin in the quality control of mitophagy, including sensing of mitochondrial distress by PINK1, activation of Parkin by PINK1 to induce mitophagy, and the physiological relevance of the PINK1–Parkin pathway. Narendra and Youle review the current understanding of the role of PINK1–Parkin in the quality control of mitophagy, highlighting the underlying mechanisms and physiological relevance of the pathway, as well as its role in neuroprotection.