PINK1-dependent recruitment of Parkin to mitochondria in mitophagy.

Show simple item record Vives-Bauza, Cristòfol Zhou, Chun Huang, Yong Cui, Mei de Vries, Rosa L.A. Kim, Jiho May, Jessica Tocilescu, Maja Aleksandra Liu, Wencheng Ko, Hans Seok Magrané, Jordi Moore, Darren J. Dawson, Valina L. Grailhe, Regis Dawson, Ted M. Li, Chenjian Tieu, Kim Przedborski, Serge 2018-10-04T11:13:11Z
dc.description.abstract Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and PARK2/Parkin mutations cause autosomal recessive forms of Parkinson's disease. Upon a loss of mitochondrial membrane potential (DeltaPsi(m)) in human cells, cytosolic Parkin has been reported to be recruited to mitochondria, which is followed by a stimulation of mitochondrial autophagy. Here, we show that the relocation of Parkin to mitochondria induced by a collapse of DeltaPsi(m) relies on PINK1 expression and that overexpression of WT but not of mutated PINK1 causes Parkin translocation to mitochondria, even in cells with normal DeltaPsi(m). We also show that once at the mitochondria, Parkin is in close proximity to PINK1, but we find no evidence that Parkin catalyzes PINK1 ubiquitination or that PINK1 phosphorylates Parkin. However, co-overexpression of Parkin and PINK1 collapses the normal tubular mitochondrial network into mitochondrial aggregates and/or large perinuclear clusters, many of which are surrounded by autophagic vacuoles. Our results suggest that Parkin, together with PINK1, modulates mitochondrial trafficking, especially to the perinuclear region, a subcellular area associated with autophagy. Thus by impairing this process, mutations in either Parkin or PINK1 may alter mitochondrial turnover which, in turn, may cause the accumulation of defective mitochondria and, ultimately, neurodegeneration in Parkinson's disease.
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dc.relation.isformatof Versió postprint del document publicat a:
dc.relation.ispartof Proceedings of the National Academy of Sciences of the United States of America, 2010, vol. 107, num. 1, p. 378-383
dc.rights (c) Vives-Bauza, Cristòfol et al., 2010
dc.subject.classification 616.8 - Neurologia. Neuropatologia. Sistema nerviós
dc.subject.other 616.8 - Neurology. Neuropathology. Nervous system
dc.title PINK1-dependent recruitment of Parkin to mitochondria in mitophagy.
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/acceptedVersion 2018-10-04T11:13:11Z
dc.rights.accessRights info:eu-repo/semantics/embargoedAccess

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