Subcomplex Ilambda specifically controls integrated mitochondrial functions in Caenorhabditis elegans.

• Main Authors: Marni J Falk, Julie R Rosenjack, Erzsebet Polyak, Wichit Suthammarak, Zhongxue Chen, Phil G Morgan, Margaret M Sedensky
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2009-08-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC2719872?pdf=render

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 Ilambda 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.