Open AccessSubcomplex Iλ Specifically Controls Integrated Mitochondrial Functions in Caenorhabditis elegans
Author(s) -
Marni J. Falk,
Julie Rosenjack,
Erzsébet Polyák,
Wichit Suthammarak,
Zhongxue Chen,
Phil G. Morgan,
Margaret M. Sedensky
Publication year - 2009
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0006607
Subject(s) - caenorhabditis elegans , biology , mitochondrion , protein subunit , gene knockdown , rna interference , mitochondrial respiratory chain , coenzyme q – cytochrome c reductase , microbiology and biotechnology , mitochondrial disease , mitochondrial dna , genetics , electron transport complex i , respiratory chain , gene , rna , cytochrome c
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.