CGC Bibliography Paper 5333

Mitochondrial contributions to aging in the nematode Caenorhabditis elegans.

Ishii N, Kita K, Hartman PS

Medline:

Citation:

Current Genomics 2: 349-355 2001

Type:

REVIEW

Genes:

clk-1 gas-1 mev-1

Abstract:

Free radicals and their sequelae figure prominently in cellular and organismal aging. Generated primarily in mitochondria as unwanted products of oxidative phosphorylation, free radicals induce a wide variety of damage that compromises molecular, cellular and organismal integrity. The free-living nematode Caenorhabditis elegans has been employed widely to explore life span. Conversely, genetic analyses of mutants that shorten life span have also provided insights into aging as it occurs in wild type. In this review we focus on three such "aging" mutants of C. elegans (mev-1, gas-1, and clk-1). Although isolated in different laboratories and using different selection criteria, all three affect aging by perturbing mitochondrial structure and/or function. gas-1 encodes a subunit of complex I, one of the five membrane-bound mitochondrial complexes that comprise the electron transport system. Originally isolated because they are hypersensitive to volatile anesthetics, gas-1 mutants were subsequently found to be hypersensitive to oxidative stress, presented in the form of either hyperoxia or methyl viologen. mev-1 encodes a subunit of complex II and was initially studied on the basis of its aging, hypermutability, abnormal mitochondrial structure, compromised DNA repair capacity and increased endogenous levels of free radicals. clk-1 encodes a protein homologous to the yeast coq7/cat5 gene product. clk-1 mutations result in reduced rates of certain developmental and behavioral phenomena as well as in an extended life span. In yeast, coq7/cat5 mutants were reported to be defective in respiration due to a deficiency in the biosynthesis of ubiquinone. It has been hypothesized that the involvement of clk-1/coq7/cat5 in ubiquinone biosynthesis is regulatory because clk-1 mutants show normal rates of mitochondrial respiration. The phenotypes of each of these three mutants will be presented, with