Silencing of ubiquinone biosynthesis genes extends life span in Caenorhabditis elegans

FASEB J. 2003 Jun;17(9):1135-7. doi: 10.1096/fj.02-1022fje. Epub 2003 Apr 22.

Abstract

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.

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans / physiology*
  • Electron Transport
  • Escherichia coli / genetics
  • Longevity / genetics*
  • Mitochondria / metabolism
  • Models, Biological
  • RNA Interference*
  • Superoxides / metabolism
  • Transformation, Bacterial
  • Ubiquinone / biosynthesis*

Substances

  • Superoxides
  • Ubiquinone
  • ubiquinone 8
  • ubiquinone 9