PINK1 protects from P...( Parkinson disease (PD) is a common neu...)

Parkinson disease (PD) is a common neurodegenerative disease characterized by the selective loss of midbrain dopaminergic neurons. Although the cause of PD is unknown, pathological analyses have suggested the involvement of oxidative stress and mitochondrial dysfunction. Recently, an inherited form of early-onset PD has been linked to mutations in both copies of the gene encoding the mitochondrial protein PINK1. Furthermore, increasing evidence indicates that single-copy mutations in PINK1 are a significant risk factor in the development of later-onset PD.

In a study published this week in the open access journal PLoS Biology, Julia Pridgeon, Lian Li, and colleagues at Emory University show that PINK1 is a protein kinase that phosphorylates the mitochondrial molecular chaperone TRAP1 to promote cell survival. The researchers find that PINK1 normally protects against oxidative-stress-induced cell death by suppressing cytochrome c release from mitochondria. The PINK1 mutations linked to PD impair the ability of PINK1 to phosphorylate TRAP1 and promote cell survival. These findings reveal a novel anti-apoptotic signaling pathway that is disrupted by mutations in PINK1. This study suggests that this pathway has a role in PD pathogenesis and may be a target for therapeutic intervention.

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Contact: Natalie Bouaravong
press@plos.org
415-568-3445
Public Library of Science
18-Jun-2007