The mitochondrial-associated proteins, Pink1 and Parkin, are frequently mutated in Parkinson’s disease (PD), but little is known about their regulation and role in pathology. Here, Alexander Whitworth, Jeffrey Lee and colleagues identify two proteases involved in this pathway in Drosophila. They find that the mitochondrial serine protease, Omi/HtrA2, is activated downstream of Pink1, and that Rhomboid-7 (the fly ortholog of human PARL) is required to process the mitochondrial-membrane-tethered forms of Pink and Omi into their soluble forms. PARL is a member of a recently discovered mitochondrial intramembrane protease family, which regulates mitochondrial morphology and apoptosis. The authors suggest that these proteins are involved in pathways linked to the premature death processes induced in the midbrain dopaminergic neurons that lead to PD.

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2008