TRAP1 rescues PINK1 loss-of-function phenotypes

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TRAP1 rescues PINK1 loss-of-function phenotypes.

PTEN-induced kinase 1 (PINK1) is a serine/threonine kinase that is localized to mitochondria. It protects cells from oxidative stress by suppressing mitochondrial cytochrome c release, thereby preventing cell death. Mutations in Pink1 cause early-onset Parkinson's disease (PD). Consistently, mitochondrial function is impaired in Pink1-linked PD patients and model systems. Previously, in vitro a...

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DJ-1 is critical for mitochondrial function and rescues PINK1 loss of function.

Mutations or deletions in PARKIN/PARK2, PINK1/PARK6, and DJ-1/PARK7 lead to autosomal recessive parkinsonism. In Drosophila, deletions in parkin and pink1 result in swollen and dysfunctional mitochondria in energy-demanding tissues. The relationship between DJ-1 and mitochondria, however, remains unclear. We now report that Drosophila and mouse mutants in DJ-1 show compromised mitochondrial fun...

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Loss of Gsx1 and Gsx2 Function Rescues Distinct Phenotypes in Dlx1/2 Mutants

Mice lacking the Dlx1 and Dlx2 homeobox genes (Dlx1/2 mutants) have severe deficits in subpallial differentiation, including overexpression of the Gsx1 and Gsx2 homeobox genes. To investigate whether Gsx overexpression contributes to the Dlx1/2 mutant phenotypes, we made compound loss-of-function mutants. Eliminating Gsx2 function from the Dlx1/2 mutants rescued the increased expression of Ascl...

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PINK1 Protects against Oxidative Stress by Phosphorylating Mitochondrial Chaperone TRAP1

Mutations in the PTEN induced putative kinase 1 (PINK1) gene cause an autosomal recessive form of Parkinson disease (PD). So far, no substrates of PINK1 have been reported, and the mechanism by which PINK1 mutations lead to neurodegeneration is unknown. Here we report the identification of TNF receptor-associated protein 1 (TRAP1), a mitochondrial molecular chaperone also known as heat shock pr...

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Loss-of-function rodent models for parkin and PINK1.

Parkinson's disease is a common neurodegenerative disorder whose aetiology is not yet fully understood. In the past ten years, the discovery of genes linked to hereditary forms of the disease has impelled the development of animal models. These should lead to the identification of novel pathways that provide insight into the functionality of the proteins involved and the pathogenesis of the spo...

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ژورنال

عنوان ژورنال: Human Molecular Genetics

سال: 2013

ISSN: 1460-2083,0964-6906

DOI: 10.1093/hmg/ddt132