Defective mitochondrial protein translocation precludes normal Caenorhabditis elegans development.
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.
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, USA.
Sean P
SP
Curran
Edward P
EP
Leverich
Carla M
CM
Koehler
Pamela L
PL
Larsen
D000818:Animals; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology
D029742:Caenorhabditis elegans Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D000226:Mitochondrial ADP, ATP Translocases