This invention includes HeLa cells that are engineered to inducibly express a mutant form of ornithine decarboxylase that is targeted to the mitochondrial matrix and forms insoluble protein aggregates. The presence of unfolded proteins in the matrix causes the accumulation of the mitochondrial kinase PINK1 and the E3 ubiquitin ligase PARK2/Parkin. These proteins play a critical role in degrading the mitochondria where they are expressed, a process call mitophagy. Mutations in these two genes are associated with familial Parkinson disease.
Prior models of PINK1/Parkin activation relied on mitochondrial depolarizing agents. This model may be more physiological and subtle, allowing a more valid way to assess compounds that increase PINK1 activity.