Hidden phenotypes of PINK1/Parkin knockout mice

PINK1, a serine/threonine ubiquitin kinase, and Parkin, an E3 ubiquitin ligase, work in coordination to target damaged mitochondria to the lysosome in a process called mitophagy. This review will cover what we have learned from PINK1 and Parkin knockout (KO) mice. Systemic PINK1 and Parkin KO mouse models haven't faithfully recapitulated early onset forms of Parkinson's disease found in humans with recessive mutations in these genes. However, the utilization of these mouse models has given us insight into how PINK1 and Parkin contribute to mitochondrial quality control and function in different tissues beyond the brain such as in heart and adipose tissue. Although PINK1 and Parkin KO mice have been generated over a decade ago, these models are still being used today to creatively elucidate cell-type specific functions. Recently, these mouse models have uncovered that these proteins contribute to innate immunity and cancer phenotypes.

Automated summary

Although PINK1 and Parkin KO mouse models do not faithfully recapitulate early onset forms of Parkinson's disease, they have provided insights into the roles of PINK1 and Parkin in mitochondrial quality control and function in various tissues beyond the brain. Despite being generated over a decade ago, these models are still being used to creatively elucidate the cell-type specific functions of these proteins. Recently, these mouse models have revealed the contributions of these proteins to innate immunity and cancer phenotypes.