Mitochondrial Biology Gets A New Chaperone

Source: Journal of Clinical Investigation
Date Posted: 2005-10-07
Web Address: http://www.sciencedaily.com/releases/2005/10/051007101150.htm

MITOCHONDRIAL BIOLOGY GETS A NEW CHAPERONE

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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