Defective mitochondrial protein translocation precludes normal Caenorhabditis elegans development

J Biol Chem. 2004 Dec 24;279(52):54655-62. doi: 10.1074/jbc.M409618200. Epub 2004 Oct 13.

Abstract

We demonstrate biochemically that the genes identified by sequence similarity as orthologs of the mitochondrial import machinery are functionally conserved in Caenorhabditis elegans. Specifically, tin-9.1 and tin-10 RNA interference (RNAi) treatment of nematodes impairs import of the ADP/ATP carrier into isolated mitochondria. Developmental phenotypes are associated with gene knock-down of the mitochondrial import components. RNAi of tomm-7 and ddp-1 resulted in mitochondria with an interconnected morphology in vivo, presumably due to defects in the assembly of outer membrane fission/fusion components. RNAi of the small Tim proteins TIN-9.1, TIN-9.2, and TIN-10 resulted in a small body size, reduced number of progeny produced, and partial embryonic lethality. An additional phenotype of the tin-9.2(RNAi) animals is defective formation of the somatic gonad. The biochemical demonstration that the protein import activity is reduced, under the same conditions that yield the defects in specific tissues and lethality in a later generation, suggests that the developmental abnormalities observed are a consequence of defects in mitochondrial inner membrane biogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans / ultrastructure
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / physiology*
  • Mitochondria / chemistry
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure
  • Mitochondrial ADP, ATP Translocases / metabolism
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology

Substances

  • Caenorhabditis elegans Proteins
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • RNA, Small Interfering
  • Mitochondrial ADP, ATP Translocases