PTEN induced kinase 1 (PINK1) (PINK1)

PTEN induced kinase 1 (PINK1) is a mitochondrial serine/threonine kinase that serves as a critical sensor of mitochondrial health and a master regulator of mitophagy (EMBO Mol Med, 2009; Frontiers in Oncology, 2022). Under normal conditions, PINK1 is imported into healthy mitochondria and rapidly degraded; however, upon mitochondrial damage or depolarization, it stabilizes on the outer mitochondrial membrane (Science, 2025; NIH, 2023). Once stabilized, PINK1 phosphorylates ubiquitin and the E3 ubiquitin ligase Parkin, triggering the selective autophagic clearance of the dysfunctional organelle (Nature, 1998; Open Biology, 2011). Mutations in the PINK1 gene (PARK6) are a primary cause of early-onset autosomal recessive Parkinson's disease, as the loss of PINK1 function leads to the accumulation of damaged mitochondria and subsequent neuronal death (Science, 2025; Brain, 2024). Therapeutic strategies targeting PINK1 include small-molecule activators like MTK458 to enhance its kinase activity and RNA-based approaches, such as mRNA editing using ADAR2 or antisense oligonucleotides, to restore functional protein levels or repair pathogenic mutations (Nucleic Acids Research, 2016; Michael J. Fox Foundation, 2023). The mRNA itself is subject to complex regulation, including transport via mitochondrial hitch-hiking and negative regulation by microRNAs like miR-27a/b (BioRxiv, 2024; NIH, 2016). Beyond neurodegeneration, PINK1 has also been implicated in cancer cell survival and chemoresistance, highlighting its broad significance in cellular homeostasis (Frontiers in Oncology, 2022; NIH, 2026).

Other names

BRPKPARK6PTEN-induced putative kinase 1

Activation of mitophagy through stabilization of PINK1 on damaged mitochondria and phosphorylation of ubiquitin and Parkin; RNA-targeted strategies include mRNA editing to repair mutations and antisense-mediated regulation of expression.