ScienceDaily (Oct. 7, 2005) — Mitochondrial complex I deficiency is one of the most common defects in patients with mitochondrial disease. The deficiency results from a failure to assemble the enzyme properly, but the nature of the molecular chaperones that are necessary for this process in mammals have remained obscure.

In a new study appearing on October 3 in The Journal of Clinical Investigation, Eric Shoubridge and colleagues McGill University identify candidate proteins involved in complex I assembly, and show that one of the candidates, B17.2L, is an assembly factor. The authors identify a null mutation in a patient with a progressive encephalopathy, and show that the defect can be functionally complemented by expression of the wild-type cDNA in patient cells. They also show that an antibody against the B17.2L protein recognizes a subassembly of complex I in several additional patients with complex I assembly defects, but not the whole enzyme complex itself, consistent with a role as a molecular chaperone.

This is the first molecular chaperone to be characterized for mammalian complex I, and is the first identification of the genetic basis of disease in a patient with a complex I assembly defect.

In a related commentary, Robert Nussbaum writes, "The research described here combines clever model organism genomics and bioinformatics to identify the first mammalian protein required for the normal assembly of complex I."

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