The L-isoaspartyl-O-methyltransferase in Caenorhabditis elegans larval longevity and autophagy.
The protein L-isoaspartyl-O-methyltransferase, coded by the pcm-1 gene in Caenorhabditis elegans, participates in the repair of age-damaged proteins. We tested the ability of pcm-1-deficient nematodes to survive starvation stress as developmentally-arrested L1 larvae. We found that pcm-1 mutant L1 larvae do not survive as well as wild-type L1 larvae when incubated in M9 medium without nutrients. We then tested whether the starved L1 larvae could continue development when allowed access to food in a recovery assay. A loss of recovery ability with age was observed for all larvae, with little or no difference between the pcm-1 mutant and wild-type N2 larvae. Interestingly, when L1 larvae were starved in cholesterol-containing S medium or M9 medium supplemented with cholesterol, the survival rates of both mutant and wild-type animals nearly doubles, with pcm-1 larvae again faring more poorly than N2 larvae. Furthermore, L1 larvae cultured in these cholesterol-containing media show an increase in Sudan Black staining over animals cultured in M9 medium. The longevity defects of pcm-1 mutants previously seen in dauer larvae and here in L1 larvae suggest a defect in the ability of pcm-1 mutants to recycle and reuse old cellular components in pathways such as autophagy. Using an autophagosomal marker, we found evidence suggesting that the pcm-1 mutation may inhibit autophagy during dauer formation, suggesting that the absence of protein repair may also interfere with protein degradation pathways.
Gomez
Tara A
TA
Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California-Los Angeles, 607 Charles E. Young Drive East, Los Angeles, CA 90095, USA. tara@caltech.edu
Banfield
Kelley L
KL
Trogler
Dorothy M
DM
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 / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism; D017238:Genes, Helminth; D007814:Larva / Q000201:enzymology; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008780:Methyltransferases / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D013217:Starvation
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002784:Cholesterol; C490112:pcm-1 protein, C elegans; D008780:Methyltransferases