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PINK Participates in Parkinson's Pathway

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Science  30 Nov 2007:
Vol. 318, Issue 5855, pp. 1353
DOI: 10.1126/science.318.5855.1353c

Mice expressing missense mutations in a serine protease known as HtrA2 (also called Omi) exhibit a neurodegenerative disease that shows similarities to Parkinson's disease in humans. Plun-Favreau et al. describe a connection between this protein and PINK1, a mitochondrial protein kinase that is mutated in certain forms of Parkinson's disease. HtrA2 functions to detect damaged or misfolded proteins caused by stress in the mitochondria. Misfolded proteins bind to a regulatory domain and activate the protease. HtrA2 may also be regulated by phosphorylation in response to the stress-activated p38 MAP (mitogen-activated protein) kinase pathway. Although PINK1 binds to HtrA2 and was required for p38-activated phosphorylation and activation of HtrA2, PINK appeared not to phosphorylate HtrA2 directly. Furthermore, phosphorylation of HtrA2 was increased in samples of brain from patients with idiopathic Parkinson's disease—as might be expected if mitochondrial stress in the diseased cells caused activation of the p38 pathway and consequent phosphorylation and activation of HtrA2. — LBR

Nat. Cell Biol. 9, 1243 (2007).

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