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.

SUMMARY The decision of stem cells to proliferate and differentiate is finely controlled. The Caenorhabditis elegans germ line provides a tractable system to study the mechanisms that control stem cell proliferation and homeostasis [1–4]. Autophagy is a conserved cellular recycling process crucial for cellular homeostasis in many different contexts [5], but its function in germline stem cell proliferation remains poorly understood. Here, we describe a function for autophagy in germline stem cell proliferation. We found that autophagy genes, such as bec-1/Beclin1, atg-16.2/ATG16L, atg-18/WIPI1/2, and atg-7/ATG7 are required for the late larval expansion of germline stem cell progenitors in the C. elegans gonad. We further show that BEC-1/Beclin1 acts independently of the GLP-1/Notch or DAF-7/TGFβ pathways, but together with the DAF-2/insulin IGF-1 receptor (IIR) signaling pathway to promote germline stem cell proliferation. Similar to DAF-2/IIR, BEC-1/Beclin1, ATG-18/WIPI1/2 and ATG-16.2/ATG16L all promote cell cycle progression, and are negatively regulated by the phosphatase and tensin DAF-18/PTEN. However, whereas BEC-1/Beclin1 acts through the transcriptional regulator SKN-1/Nrf1, ATG-18/WIPI1/2 and ATG-16.2/ATG16L exert their function through the DAF-16/FOXO transcription factor. In contrast, ATG-7 functions in concert with the DAF-7/ TGFβ pathway to promote germline proliferation, and is not required for cell cycle progression. Finally, we report that BEC-1/Beclin1 functions cell non-autonomously to facilitate cell cycle progression and stem cell proliferation. Our findings demonstrate a novel non-autonomous role for BEC-1/Beclin1 in the control stem cell proliferation, and cell cycle progression, which may have implications for the understanding, and development, of therapies against malignant cell growth in the future.

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Myosin V–mediated cargo transport ensures that organelles are correctly positioned in cells, an essential process for cellular function. In this study, Yau et al. show that the p21-activated kinase Cla4 spatially regulates the release of a myosin V cargo.

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