PINK1

The PINK1 gene produces a protein called PTEN induced putative kinase 1. This protein is found in cells throughout the body, with highest levels in the heart, muscles, and testes. Within cells, the protein is located in the mitochondria, the energy-producing centers that provide power for cellular activities. The function of PTEN induced putative kinase 1 is not fully understood. It appears to help protect mitochondria from malfunctioning during periods of cellular stress, such as unusually high energy demands.

Researchers believe that two specialized regions of PTEN induced putative kinase 1 are essential for the protein to function properly. One region, called the mitochondrial-targeting motif, serves as a delivery address. The protein is produced outside the mitochondria, and this motif helps ensure that it is delivered to the mitochondria. Another region, called the kinase domain, probably carries out the protein's protective function.

Parkinson disease - caused by mutations in the PINK1 gene

Researchers have identified more than 20 PINK1 mutations that cause early-onset Parkinson disease. Some mutations change one of the protein building blocks (amino acids) used to make PTEN induced putative kinase 1. Other mutations lead to an abnormally small version of the protein.

Many PINK1 mutations alter or eliminate the kinase domain, leading to a loss of protein function. At least one mutation affects the mitochondrial-targeting motif and may disrupt delivery of the protein to mitochondria. With reduced or absent PTEN induced putative kinase 1 activity, mitochondria may malfunction, particularly when cells are stressed. Cells can die if power is not provided for essential activities. It is unclear how PINK1 mutations cause the selective death of nerve cells that characterizes Parkinson disease.