The Parkinson’s disease related PINK1 Kinase shuttles through mitochondria during processing as revealed by superresolution microscopy

Abstract

The cytosolic phosphatase and tensin homolog Pten-kinase PINK1 is a sensor for mitochondrial de-energization and an activator in the elimination process of impaired mitochondria by mitophagy. On the other hand, PINK1 to short form is involved in this process. We here show by means of triple-color superresolution microscopy in live cells for the first time that PINK1 is fully imported into energized but not de-energized mitochondria, cleaved inside and released into the cytosol again. During this shuttling between cytosol and the interior of mitochondria, the kinase domain has access to different mitochondrial microcompartments enabling the interaction with mitochondrial chaperone TNF receptor-associated protein 1 (TRAP1) inside mitochondria, mitochondrial protease Htr2a and probably subunit NdufA10 of complex one as observed before. Thus, these findings finally give the molecular base for the multiple functions of PINK1 - inside energized mitochondria and outside of de-energized mitochondria.