title: Mitochondrial respiratory chain deficiency in Caenorhabditis elegans results in developmental arrest and increased life span.
abstract: The growth and development of Caenorhabditis elegans are energy-dependent and rely on the mitochondrial respiratory chain (MRC) as the major source of ATP. The MRC is composed of approximately 70 nuclear and 12 mitochondrial gene products. Complexes I and V are multisubunit proteins of the MRC. The nuo-1 gene encodes the NADH- and FMN-binding subunit of complex I, the NADH-ubiquinone oxidoreductase. The atp-2 gene encodes the active-site subunit of complex V, the ATP synthase. The nuo-1(ua1) and atp-2(ua2) mutations are both lethal. They result in developmental arrest at the third larval stage (L3), arrest of gonad development at the second larval stage (L2), and impaired mobility, pharyngeal pumping, and defecation. Surprisingly, the nuo-1 and atp-2 mutations significantly lengthen the life spans of the arrested animals. When MRC biogenesis is blocked by chloramphenicol or doxycycline (inhibitors of mitochondrial translation), a quantitative and homogeneous developmental arrest as L3 larvae also results. The common phenotype induced by the mutations and drugs suggests that the L3-to-L4 transition may involve an energy-sensing developmental checkpoint. Since approximately 200 gene products are needed for MRC assembly and mtDNA replication, transcription, and translation, we predict that L3 arrest will be characteristic of mutations in these genes.
authors: Canadian Institutes of Health Research Group in the Molecular Biology of Membrane Proteins, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors: W Y
authors: WY
authors: Tsang
authors: L C
authors: LC
authors: Sayles
authors: L I
authors: LI
authors: Grad
authors: D B
authors: DB
authors: Pilgrim
authors: B D
authors: BD
authors: Lemire
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017931:DNA Primers; D004579:Electron Transport; D017238:Genes, Helminth
chemical_list: D017931:DNA Primers