Skip to content
Back to glossary
Cell biology

Parkin (PRKN/PARK2)

Parkin, encoded by the PRKN gene (formerly PARK2), is an E3 ubiquitin ligase. It is a RING-between-RING type. It sits at the center of mitochondrial quality control. In the cytosol, Parkin is normally held in a self-inhibited, folded-up shape. The trigger to wake it is PINK1. PINK1 builds up on a damaged mitochondrion, one of the tiny power plants in your cells. There, it phosphorylates ubiquitin and Parkin's ubiquitin-like (Ubl) domain at Ser65. That releases the self-inhibition. And it recruits Parkin to the outer mitochondrial membrane. Active Parkin then builds ubiquitin chains on outer-membrane targets. These chains are rich in K6, K11, and K63 linkages. The targets include MFN1/2, MIRO, and VDAC1. Those chains attract autophagy receptors, including OPTN, NDP52, and p62. The result: an autophagosome engulfs the whole damaged mitochondrion. Loss-of-function PRKN mutations cause an inherited, juvenile form of Parkinson's. That directly links broken mitophagy to neurodegeneration.

Last reviewed:

This definition is educational and is not medical advice, a diagnosis, or treatment. Talk to a doctor about any health decisions. Read our full medical disclaimer

Sources

  1. Kitada T, Asakawa S, Hattori N, et al.. (1998). Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. *Nature*doi:10.1038/33416
  2. Narendra D, Tanaka A, Suen DF, Youle RJ. (2008). Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. *Journal of Cell Biology*doi:10.1083/jcb.200809125
  3. Pickrell AM, Youle RJ. (2015). The Roles of PINK1, Parkin, and Mitochondrial Fidelity in Parkinson's Disease. *Neuron*doi:10.1016/j.neuron.2014.12.007