Parkin and mitochondrial signalling

Aging, toxic chemicals and changes to the cellular environment are sources of oxidative damage to mitochondria which contribute to neurodegenerative conditions including Parkinson's disease. To counteract this, cells have developed signalling mechanisms to identify and remove select proteins and unhealthy mitochondria to maintain homeostasis. Two important proteins that work in concert to control mitochondrial damage are the protein ki-nase PINK1 and the E3 ligase parkin. In response to oxidative stress, PINK1 phosphorylates ubiquitin present on proteins at the mitochondrial surface. This signals the translocation of parkin, accelerates further phosphory-lation, and stimulates ubiquitination of outer mitochondrial membrane proteins such as Miro1/2 and Mfn1/2. The ubiquitination of these proteins is the key step needed to target them for degradation via the 26S protea-somal machinery or eliminate the entire organelle through mitophagy. This review highlights the signalling mechanisms used by PINK1 and parkin and presents several outstanding questions yet to be resolved.

Automated summary

Aging, toxic chemicals, and changes to cellular environment cause oxidative damage to mitochondria, contributing to neurodegenerative diseases like Parkinson's. To maintain homeostasis, cells use signaling mechanisms involving PINK1 and parkin to identify and remove damaged proteins and mitochondria. PINK1 phosphorylates ubiquitin on mitochondrial proteins in response to oxidative stress, leading to parkin translocation, further phosphorylation, and ubiquitination of outer mitochondrial membrane proteins. This ubiquitination is crucial in targeting proteins for degradation or eliminating the whole organelle via mitophagy.