A complex II defect affects mitochondrial structure, leading to ced-3- and ced-4-dependent apoptosis and aging.
The mev-1(kn1) mutation of Caenorhabditis elegans is in Cyt-1, which encodes a subunit of succinate-coenzyme Q oxidoreductase in the mitochondrial electron transport chain. Mutants are hypersensitive to oxidative stress and age precociously in part because of increased superoxide anion production. Here, we show that mev-1 mutants are defective in succinate-coenzyme Q oxidoreductase, possess ultrastructural mitochondrial abnormalities (especially in muscle cells), show a loss of membrane potential, have altered CED-9 and Cyt-1 protein levels under hyperoxia, and contain ced-3-and ced-4-dependent supernumerary apoptotic cells. These defects likely explain the failure of mev-1 to complete embryonic development under hyperoxia as well as its reduced life span.
Senoo-Matsuda
Nanami
N
Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
Hartman
Philip S
PS
Akatsuka
Akira
A
Yoshimura
Shinichi
S
Ishii
Naoaki
N
D000375:Aging; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D003580:Cytochromes / Q000235:genetics*; D045303:Cytochromes b; D000860:Hypoxia; D007150:Immunohistochemistry; D008564:Membrane Potentials; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D010100:Oxygen / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D013997:Time Factors
D000911:Antibodies, Monoclonal; D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C089224:Ced-4 protein, C elegans; C087233:Ced-9 protein, C elegans; D003580:Cytochromes; C472666:MEV-1 protein, C elegans; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D045303:Cytochromes b; D020169:Caspases; C089223:ced-3 protein, C elegans; D010100:Oxygen