Mitochondrial Biology Gets A New Chaperone
- Date:
- October 7, 2005
- Source:
- Journal of Clinical Investigation
- Summary:
- Mitochondrial complex I deficiency is a common defect in patients with mitochondrial disease. The deficiency results from a failure to assemble the enzyme properly, but the molecular chaperones necessary for this process have remained obscure. A JCI study now identifies the first molecular chaperone for mammalian complex I, and provides the first identification of the genetic basis of disease in a patient with a complex I assembly defect. A related commentary accompanies.
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Mitochondrial complex I deficiency is one of the most common defects inpatients with mitochondrial disease. The deficiency results from afailure to assemble the enzyme properly, but the nature of themolecular chaperones that are necessary for this process in mammalshave remained obscure.
In a new study appearing on October 3 in The Journal of ClinicalInvestigation, Eric Shoubridge and colleagues McGill Universityidentify candidate proteins involved in complex I assembly, and showthat one of the candidates, B17.2L, is an assembly factor. The authors identify a null mutation in a patient with aprogressive encephalopathy, and show that the defect can befunctionally complemented by expression of the wild-type cDNA inpatient cells. They also show that an antibody against the B17.2Lprotein recognizes a subassembly of complex I in several additionalpatients with complex I assembly defects, but not the whole enzymecomplex itself, consistent with a role as a molecular chaperone.
This is the first molecular chaperone to be characterized for mammaliancomplex I, and is the first identification of the genetic basis ofdisease in a patient with a complex I assembly defect.
In a related commentary, Robert Nussbaum writes, "The researchdescribed here combines clever model organism genomics andbioinformatics to identify the first mammalian protein required for thenormal assembly of complex I."
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