A defect in the cytochrome b large subunit in complex II causes both superoxide anion overproduction and abnormal energy metabolism in Caenorhabditis elegans.
A mev-1(kn1) mutant of the nematode Caenorhabditis elegans is defective in the cytochrome b large subunit (Cyt-1/ceSDHC) in complex II of the mitochondrial electron transport chain. We have previously shown that a mutation in mev-1 causes shortened life span and rapid accumulation of aging markers such as fluorescent materials and protein carbonyls in an oxygen-dependent fashion. However, it remains unclear as to whether this hypersensitivity is caused by direct toxicity of the exogenous oxygen or by the damage of endogenous reactive oxygen species derived from mitochondria. Here we report important biochemical changes in mev-1 animals that serve to explain their abnormalities under normoxic conditions: (i) an overproduction of superoxide anion from mitochondria; and (ii) a reciprocal reduction in glutathione content even under atmospheric oxygen. In addition, unlike wild type, the levels of superoxide anion production from mev-1 mitochondria were significantly elevated under hyperoxia. Under normal circumstances, it is well known that superoxide anion is produced at complexes I and III in the electron transport system. Our data suggest that the mev-1(kn1) mutation increases superoxide anion production at complex II itself rather than at complexes I and III. The mev-1 mutant also had a lactate level 2-fold higher than wild type, indicative of lactic acidosis, a hallmark of human mitochondrial diseases. These data indicate that Cyt-1/ceSDHC plays an important role not only in energy metabolism but also in superoxide anion production that is critically involved in sensitivity to atmospheric oxygen.
Senoo-Matsuda
N
N
Department of Molecular Life Science and Department of Physiology, Tokai University School of Medicine, Ishehara, Kanagawa 259-1193, Japan.
Yasuda
K
K
Tsuda
M
M
Ohkubo
T
T
Yoshimura
S
S
Nakazawa
H
H
Hartman
P S
PS
Ishii
N
N
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D002952:Citric Acid Cycle; D003573:Cytochrome b Group / Q000737:chemistry*; D042963:Electron Transport Complex II; D004734:Energy Metabolism; D005978:Glutathione / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009097:Multienzyme Complexes / Q000737:chemistry*; D009154:Mutation; D010088:Oxidoreductases / Q000737:chemistry*; D011487:Protein Conformation; D021122:Protein Subunits; D013385:Succinate Dehydrogenase / Q000737:chemistry*; D013481:Superoxides / Q000378:metabolism*
D003573:Cytochrome b Group; D009097:Multienzyme Complexes; D021122:Protein Subunits; D013481:Superoxides; D000255:Adenosine Triphosphate; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D005978:Glutathione