In 1998, PARKIN was reported as a causal gene for hereditary recessive Parkinsonism by Kitada, Mizuno, Hattori, and Shimizu et al. Later in 2004, PINK1 was also reported as a causal gene for hereditary recessive Parkinsonism by Valente, Auburger, and Wood et al. Although many unsolved mysteries still remain, our knowledge of PINK1 and Parkin function has increased dramatically since then. Despite a number of milestone studies that advanced the PINK1 and Parkin research field, a critical turning point was undoubtedly the determination that their genuine subcellular localization was on depolarized mitochondria. In this review, we outline the key studies that have contributed to our current model for mitochondrial localization of PINK1 and Parkin. Interestingly, like two sides of a coin, our attempts to elucidate the mechanisms underlying the localization of PINK1 and Parkin were inextricably tied to the identification of the PINK1 substrate and molecular dissection of the Parkin activation mechanism.
Keywords: Mitochondria; PINK1; Parkin; Parkinson's disease; Selective localization.
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
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