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The role of PINK1–Parkin in mitochondrial quality control

Nature Cell Biology volume 26, pages 1639–1651 (2024)Cite this article

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Abstract

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.

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Fig. 1: PINK1–Parkin-mediated mitophagy.
Fig. 2: The structural basis of PINK1-mediated phosphorylation of ubiquitin and Parkin activation by phospho-ubiquitin.
Fig. 3: PINK1 life cycle in sensing of mitochondrial damage.
Fig. 4: Voltage sensing by PINK1 across the IMM and OMM.

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Acknowledgements

This work was supported by the Intramural Research Program of the NINDS, National Institutes of Health.

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  1. Mitochondrial Biology and Neurodegeneration Unit, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

    Derek P. Narendra

  2. Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

    Richard J. Youle

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D.P.N. and R.J.Y. wrote the initial and final drafts and generated the figures.

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Narendra, D.P., Youle, R.J. The role of PINK1–Parkin in mitochondrial quality control. Nat Cell Biol 26, 1639–1651 (2024). https://doi.org/10.1038/s41556-024-01513-9

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