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

Sanford-Burnham Medical Research Institute
Autophagy (Impact Factor: 11.75). 01/2013; 9(3). DOI: 10.4161/auto.22930
Source: PubMed


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
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    • "Surprisingly, in laboratory conditions C. elegans can overcome the complete loss of the perilipin-related protein W01A8.1, presumably by activating perilipin-independent lipid degradation. Previous work has shown that an additional lipid degradation pathway, autophagy, was important for lipid metabolism in C. elegans (Lapierre et al., 2013), mammals (Singh et al., 2009) as well as in yeast (Van Zutphen et al., 2014). Similarly in Drosophila, which has two perilipins (plin1 and plin2), the double mutants are viable but have small lipid droplets. "
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