Carroll J, Shannon RJ, Fearnley IM, Walker JE, Hirst J (2002...

来自 : www.oalib.com/references/14870 发布时间：2021-03-25

ABSTRACT: Complex I dysfunction is a common, heterogeneous cause of human mitochondrial disease having poorly understood pathogenesis. The extensive conservation of complex I composition between humans and Caenorhabditis elegans permits analysis of individual subunit contribution to mitochondrial functions at both the whole animal and mitochondrial levels. We provide the first experimentally-verified compilation of complex I composition in C. elegans, demonstrating 84% conservation with human complex I. Individual subunit contribution to mitochondrial respiratory capacity, holocomplex I assembly, and animal anesthetic behavior was studied in C. elegans by RNA interference-generated knockdown of nuclear genes encoding 28 complex I structural subunits and 2 assembly factors. Not all complex I subunits directly impact respiratory capacity. Subcomplex Iλ subunits along the electron transfer pathway specifically control whole animal anesthetic sensitivity and complex II upregulation, proportionate to their relative impairment of complex I-dependent oxidative capacity. Translational analysis of complex I dysfunction facilitates mechanistic understanding of individual gene contribution to mitochondrial disease. We demonstrate that functional consequences of complex I deficiency vary with the particular subunit that is defective.
Carroll J, Shannon RJ, Fearnley IM, Walker JE, Hirst J (2002) Definition of the nuclear encoded protein composition of bovine heart mitochondrial complex...Carroll J, Shannon RJ, Fearnley IM, Walker JE, Hirst J (2002) Definition of the nuclear encoded protein composition of bovine heart mitochondrial complex I. Identification of two new subunits. J Biol Chem 277: 50311–50317.Carroll J, Shannon RJ, Fearnley IM, Walker JE, Hirst J (2002) Definition of the nuclear encoded protein composition of bovine heart mitochondrial complex I. Identification of two new subunits. J Biol Chem 277: 50311–50317.Carroll J, Shannon RJ, Fearnley IM, Walker JE, Hirst J (2002) Definition of the nuclear encoded protein composition of bovine heart mitochondrial complex I. Identification of two new subunits. J Biol Chem 277: 50311–50317.