Disease relevance of mev-1

• Mutations in the mev-1 and gas-1 genes of the nematode Caenorhabditis elegans render animals hypersensitive to oxygen and paraquat, and lead to premature aging [1].
• The mev-1 mutation in the Caenorhabditis elegans gene encoding the homolog of the SDHC subunit results in premature aging and hypersensitivity to oxidative stress [2].
• 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 [3].
• We also show that mutation frequencies were higher in the mev-1 mutant under hypoxia than in the wild type strain [4].

High impact information on mev-1

• We found that the ability of complex II to catalyse electron transport from succinate to ubiquinone is compromised in mev-1 animals [5].
• Our results indicate that mev-1 governs the rate of ageing by modulating the cellular response to oxidative stress [5].
• We show here that mev-1 encodes a subunit of the enzyme succinate dehydrogenase cytochrome b, which is a component of complex II of the mitochondrial electron transport chain [5].
• These defects likely explain the failure of mev-1 to complete embryonic development under hyperoxia as well as its reduced life span [6].
• We mutated Pro-190 of the yeast Sdh2p subunit to Gln (P190Q) and recreated the C. elegans mev-1 mutation by converting Ser-94 in the Sdh3p subunit into a glutamate residue (S94E) [2].

Chemical compound and disease context of mev-1

• A mev-1 (kn1) mutant of Caenorhabditis elegans, isolated on the basis of its methyl viologen (paraquat) hypersensitivity, is also hypersensitive to elevated oxygen levels [7].

Biological context of mev-1

• The daf-16 phenotype resembles that of mev-1 showing a short life and oxygen sensitivity [8].
• Effect of oxidative stress on translocation of DAF-16 in oxygen-sensitive mutants, mev-1 and gas-1 of Caenorhabditis elegans [1].
• Since both gas-1 and mev-1 encode subunits of electron transport chain complexes, these data illustrate how mitochondrial perturbations can impact signal transduction pathways [1].
• A mev-1 mutation in the cytochrome b large subunit (SDHC) of complex II results in superoxide anion (O2-) overproduction and therefore leads to apoptosis and precocious aging in the nematode Caenorhabditis elegans [9].

Anatomical context of mev-1

• 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 [3].
• To extend these data, a transgenic mouse cell line was constructed with a homologous mutation to mev-1 [9].

Associations of mev-1 with chemical compounds

• A methyl viologen (paraquat)-sensitive mutant, mev-1 (LG III), in Caenorhabditis elegans was about 4 times more sensitive to methyl viologen than the wild type [10].
• We also show that CoQ(10) but not Vitamin E reduced superoxide anion levels in wild type and mev-1 [11].

Physical interactions of mev-1

• In the nematode Caenorhabditis elegans, mutations have been previously isolated that affect the activities of Complex I (gas-1) and Complex II (mev-1), two of the five membrane-bound complexes that control electron flow in mitochondrial respiration [12].

Other interactions of mev-1

• The feeding method was employed to deliver dsRNA from the fourth subunit (ceSDHA) to wild-type, mev-1 (mutated in ceSDHC of complex II), and gas-1 animals (mutated in a complex I gene) [13].
• Lifespans of gas-1 and mev-1 were decreased compared with N2, while that of clk-1 was increased [14].
• We also demonstrate synthetic genetic interaction between frh-1 and mev-1, the gene encoding the succinate dehydrogenase cytochrome b subunit of complex II in mitochondria, suggesting a possible role of the C. elegans frataxin in the electron transport chain; thus, the respiratory chain might be involved in the pathogenesis of the disease [15].

References