The PINK1 gene is located on chromosome 1 in humans and encodes a protein that is synthesized as a 63 kDa precursor. This precursor is often cleaved by the mitochondrial protease PARL into a 53 kDa fragment . The PINK1 protein contains several important domains:
PINK1 is intimately involved in mitochondrial quality control. Under normal conditions, healthy mitochondria import PINK1 into the inner membrane, where it is cleaved and degraded. However, in damaged mitochondria, PINK1 accumulates on the outer membrane. This accumulation recruits another protein called parkin, which tags the damaged mitochondria for degradation through a process known as mitophagy .
PINK1’s activity is crucial for maintaining mitochondrial health. It phosphorylates various mitochondrial proteins, including parkin and ubiquitin, to coordinate the removal and replacement of dysfunctional mitochondrial components . This process helps prevent the accumulation of damaged mitochondria, which can lead to cellular stress and apoptosis.
Mutations in the PINK1 gene are associated with autosomal recessive early-onset Parkinson’s disease. These mutations impair the protein’s ability to protect mitochondria, leading to the accumulation of damaged mitochondria and neuronal cell death . This connection highlights the importance of PINK1 in maintaining neuronal health and preventing neurodegenerative diseases.
Recombinant PINK1 refers to the protein produced through recombinant DNA technology, which involves inserting the PINK1 gene into a suitable expression system to produce the protein in large quantities. This recombinant protein is used in various research applications to study its function, mechanism, and role in disease .