Autophagy and insulin/TOR signaling in Caenorhabditis elegans pcm-1 protein repair mutants.
Biological responses due to nutrient deprivation in the nematode Caenorhabditis elegans, including L1 diapause and autophagy during dauer formation, can be mediated through the linked DAF-2/insulin/IGF receptor and target-of-rapamycin (TOR) kinase pathways. Here we discuss how altered insulin/TOR signaling may underlie the previously reported phenotypes of worms with a null mutation in the pcm-1 gene that results in reduced autophagy during dauer formation and decreased L1 arrest survival. PCM-1 encodes a protein repair methyltransferase and mutants of the encoding pcm-1 gene are incapable of converting spontaneously damaged l-isoaspartyl residues in cellular proteins to normal forms by this pathway. We speculate that PCM-1 may function either directly or indirectly as an inhibitor of insulin/TOR signaling, perhaps in a role to balance autophagy with alternative protein degradation pathways that may be more specific for recognizing age-damaged proteins.
Gomez
Tara A
TA
Department of Chemistry and Biochemistry, Molecular Biology Institute, University of California, Los Angeles, California 90095, USA.
Clarke
Steven G
SG
D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000502:physiology; D017238:Genes, Helminth; D007004:Hypoglycemic Agents / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007814:Larva / Q000201:enzymology; D008136:Longevity; D008780:Methyltransferases / Q000235:genetics* / Q000502:physiology; D008954:Models, Biological; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; C490112:pcm-1 protein, C elegans; D008780:Methyltransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C472494:let-363 protein, C elegans