The intestinal cells of C. elegans are filled with heterogeneous granular organelles, intestinal granules, including lipid droplets and HEBE (HAF-4/HAF-9-enriched body evanescent with age) granules. They seem to be related with certain functions of the organ. Gut granules, lysosome-related organelles, are another subset of intestinal granules, a minor population of which has birefringency at the adult stage under a normal physiological condition. We found that the feeding RNAi of
cdc-48.1 and
cdc-48.2 resulted in the prominent accumulation of birefringent intestinal granules when RNAi clones with full-length coding DNA sequences were used. CDC-48.1 and CDC-48.2 are homologs of
p97/VCP (valosin-containing protein), a chaperone protein involved in a variety of cellular processes including the degradation of ubiquitylated proteins. Mutations in the human
p97 gene have been shown to cause multisystem proteinopathy such as amyotrophic lateral sclerosis. Here, quantitative RT-PCR analyses revealed that the RNAi of one of the
cdc-48 genes knocked down not only the target gene but also the other paralogous gene in a submaximal manner by off-target effect. Because the single mutants of these two genes did not show the phenotype, these results suggest that CDC-48.1 and CDC-48.2 are redundantly required for preventing the accumulation of birefringent materials in the intestinal granules. The tissue-specific RNAi experiments demonstrated that the knockdown of intestinal
cdc-48.1 and
cdc-48.2 is responsible for the phenocopy. To clarify the mechanisms underlying the accumulation of birefringent granules by the
cdc-48 RNAi, we then analyzed the effect of the RNAi on the mutants with deficiency of the biogenesis of gut granules or endo-lysosomal pathway. As a result, gut granule loss (glo) mutants (Hermann GJ et al. 2005) did not generate any birefringent granules even after the
cdc-48 RNAi. Moreover, defects in the late-endosomal/lysosomal pathway (
rab-7 and
tub-1), but not in the early-endosomal one (
rab-10 and
tbc-2), suppressed the accumulation of birefringent granules, indicating that the
cdc-48-knockdown-dependent accumulation of birefringent materials is modulated by the late-endosomal/lysosomal factors.