Journal
HUMAN MOLECULAR GENETICS
Volume 21, Issue 5, Pages 991-1003Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddr530
Keywords
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Funding
- [08105650]
- [23791010]
- Grants-in-Aid for Scientific Research [23791010, 23500428, 22659097, 19059010, 21390298] Funding Source: KAKEN
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Parkin is a multifunctional protein, including maintaining mitochondrial homeostasis. Recent evidence suggests that Parkin is recruited from the cytoplasm to damaged mitochondria with low membrane potential. We found that intracellular localization of Parkin changed with cellular growth phase. Parkin was preferentially localized in the mitochondria of cultured cells. The mitochondria with large amounts of Parkin showed preserved membrane potentials even during treatment with carbonyl cyanide m-chlorophenylhydrazone. Here we report a novel protein named Klokin 1 that transports Parkin to the mitochondria. Klokin 1 was localized to the mitochondria and enhanced mitochondrial expression of Parkin. Klokin 1 enhanced cell viability in Parkin-silenced cells. Klokin 1 expression was enhanced in the brains of Parkin-deficient mice but not in an autopsied PARK2 brain. Our findings indicate that mitochondrial Parkin prevents mitochondrial depolarization and that Klokin 1 may compensate for Parkin deficiency.
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