Autophagy genes are required for normal lipid levels in C. elegans

Sanford-Burnham Medical Research Institute
Autophagy (Impact Factor: 11.42). 01/2013; 9(3). DOI: 10.4161/auto.22930
Source: PubMed

ABSTRACT Autophagy is a cellular catabolic process in which various cytosolic components are degraded. For example, autophagy can mediate lipolysis of neutral lipid droplets. In contrast, we here report that autophagy is required to facilitate normal levels of neutral lipids in C. elegans. Specifically, by using multiple methods to detect lipid droplets including CARS microscopy, we observed that mutants in the gene bec- 1 (VPS30/ATG6/BECN1), a key regulator of autophagy, failed to store substantial neutral lipids in their intestines during development. Moreover, loss of bec-1 resulted in a decline in lipid levels in daf-2 [insulin/IGF-1 receptor (IIR) ortholog] mutants and in germline-less glp-1/Notch animals, both previously recognized to accumulate neutral lipids and have increased autophagy levels. Similarly, inhibition of additional autophagy genes, including unc-51/ULK1/ATG1 and lgg-1/ATG8/MAP1LC3A/LC3 during development, led to a reduction in lipid content. Importantly, the decrease in fat accumulation observed in animals with reduced autophagy did not appear to be due to a change in food uptake or defecation. Taken together, these observations suggest a broader role for autophagy in lipid remodeling in C. elegans.

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Available from: Louis Rene Lapierre, Aug 13, 2015
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    • "observations in mammalian systems, inactivation of autophagy genes in C. elegans results in enhanced staining of gut granules or lysosome related organelles during fasting (Huang et al., 2014). In contrast to this though, it has been reported that inactivation of autophagy genes in C. elegans results in reduction of lipid stores when assessed by other methods (Lapierre et al., 2013b). The precise mechanistic reasons for these opposite outcomes are not yet clear. "
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    • "It was reported that the mammalian homolog, Spinster, regulates autophagy and lysosome reformation in NRK cells. Most recently, several autophagy genes were found to be required for lipid remodeling in C. elegans (Lapierre et al., 2013). It is likely that C13C4.5 may also regulate autophagy by interfering with the morphology and function of lysosomes and subsequent fat storage and lipid metabolism. "
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