PINK1, also known as PTEN-induced kinase 1, is a serine/threonine-protein kinase in mitochondria. It is crucial for mitochondrial quality control, especially in the regulation of mitophagy, a process that selectively degrades defective mitochondria [1,2,3,4,5,8,9]. PINK1 mainly functions in the PINK1/Parkin pathway, which is essential for many aspects of mitochondrial physiology [1,2,3,4,5]. Mitochondrial health is vital for cell survival, particularly in energy-intensive neuronal cells, and PINK1's role in maintaining this health has broad biological importance [1].

Loss-of-function mutations in PINK1 cause parkinsonism in humans and mitochondrial dysfunction in model organisms [7]. In Drosophila melanogaster, genetic epistasis between PINK1 and Parkin was biochemically explained by the finding that PINK1 accumulation on mitochondria is both necessary and sufficient for Parkin recruitment to mitochondria, and disease-causing mutations in PINK1 disrupt Parkin-induced mitophagy [7]. In cultured human fibroblasts and induced pluripotent stem cell-derived neurons with homozygous PARK7 mutations, DJ-1 was found to be an essential downstream mediator in PINK1/parkin-dependent mitophagy, suggesting disruption of this pathway as a common pathogenic mechanism in autosomal recessive Parkinson's disease [6]. In mouse models, Pink1 -/- mice showed a significant decrease in bone mass and collagen deposition after ovariectomy, with inhibited osteoblast differentiation due to impaired mitochondrial homeostasis, indicating PINK1's role in bone disease [8].

In conclusion, PINK1 is a key regulator of mitochondrial quality control, mainly through its role in the PINK1/Parkin-mediated mitophagy pathway. Studies using gene knockout models, such as in Drosophila and mice, have revealed its importance in neurodegenerative diseases like Parkinson's disease and in bone diseases. Understanding PINK1's function provides insights into the mechanisms of these diseases and potential therapeutic targets.