The L-isoaspartyl-O-methyltransferase in Caenorhabditis elegans larval longevity and autophagy.

Authors: Gomez TA; Banfield KL; Trogler DM; Clarke SG

Abstract: 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.

Keywords: Animals; Autophagy/genetics/*physiology; Caenorhabditis elegans/enzymology/genetics/growth & development/*physiology; Caenorhabditis elegans Proteins/genetics/*physiology; Cell Cycle Proteins/genetics/*physiology; Cholesterol/metabolism; Genes, Helminth; Larva/enzymology; Longevity/genetics/*physiology; Methyltransferases/genetics/*physiology; Mutation; Starvation
Journal: Developmental biology
Volume: 303
Issue: 2
Pages: 493-500
Date: Dec. 26, 2006
PMID: 17187774
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Citation:

Gomez TA, Banfield KL, Trogler DM, Clarke SG (2007) The L-isoaspartyl-O-methyltransferase in Caenorhabditis elegans larval longevity and autophagy. Developmental biology 303: 493-500.


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