Silencing of ubiquinone biosynthesis genes extends life span in Caenorhabditis elegans.
Ubiquinone (coenzyme Q; Q) is a key factor in the mitochondria electron transport chain, but it also functions as an antioxidant and as a cofactor of mitochondrial uncoupling proteins. Furthermore, Q isoforms balance in Caenorhabditis elegans is determined by both dietary intake and endogenous biosynthesis. In the absence of synthesis, withdrawal of dietary Q8 in adulthood extends life span. Thus, Q plays an important role in the aging process and understanding its synthesis acquires a new impetus. We have identified by RNA interference (RNAi) eight genes, including clk-1, involved in ubiquinone biosynthesis in C. elegans feeding animals with dsRNA-containing Escherichia coli HT115 strains. Silenced C. elegans showed lower levels of both endogenous Q9 and Q8 provided by diet, produced less superoxide without a significant modification of mitochondrial electron chain, and extended life span compared with non-interfered animals. E. coli strains harboring dsRNA also interfered with their own Q8 biosynthesis. These findings suggest that more efficient electron transport between a lower amount of Q and electron transport capacity of the mitochondrial complexes leads to less production of reactive oxygen species that contributes to extension of life span in the nematode C. elegans.
Asencio
Claudio
C
Laboratorio Andaluz de Biología, Departamento de Ciencias Ambientales, Universidad Pablo de Olavide, Ctra. Utrera, Km. 1, E-41013 Sevilla, Spain. pnavas@dex.upo.es
Rodríguez-Aguilera
Juan C
JC
Ruiz-Ferrer
Macarena
M
Vela
Jordana
J
Navas
Plácido
P
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D004579:Electron Transport; D004926:Escherichia coli / Q000235:genetics; D008136:Longevity / Q000235:genetics*; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D034622:RNA Interference; D013481:Superoxides / Q000378:metabolism; D014169:Transformation, Bacterial; D014451:Ubiquinone / Q000096:biosynthesis*
D013481:Superoxides; D014451:Ubiquinone; C030778:ubiquinone 8; C030571:ubiquinone 9