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Long-term autophagy is sustained by activation of CCTβ3 on lipid droplets
  1. 1.

    Mizushima, N., Yoshimori, T. & Ohsumi, Y. The role of Atg proteins in autophagosome formation. Annu. Rev. Cell Dev. Biol. 27, 107–132 (2011).

    CAS  PubMed  Google Scholar 

  2. 2.

    Bento, C. F. et al. Mammalian autophagy: How does it work? Annu. Rev. Biochem. 85, 685–713 (2016).

    CAS  PubMed  Google Scholar 

  3. 3.

    Dikic, I. & Elazar, Z. Mechanism and medical implications of mammalian autophagy. Nat. Rev. Mol. Cell Biol. 19, 349–364 (2018).

    CAS  PubMed  Google Scholar 

  4. 4.

    Hurley, J. H. & Young, L. N. Mechanisms of autophagy initiation. Annu. Rev. Biochem. 86, 225–244 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Nakatogawa, H. Mechanisms governing autophagosome biogenesis. Nat. Rev. Mol. Cell Biol. 21, 439–458 (2020).

  6. 6.

    Axe, E. L. et al. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J. Cell Biol. 182, 685–701 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Ge, L., Melville, D., Zhang, M. & Schekman, R. The ER-Golgi intermediate compartment is a key membrane source for the LC3 lipidation step of autophagosome biogenesis. Elife 2, e00947 (2013).

    PubMed  PubMed Central  Google Scholar 

  8. 8.

    Hailey, D. W. et al. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 141, 656–667 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Hamasaki, M. et al. Autophagosomes form at ER-mitochondria contact sites. Nature 495, 389–393 (2013).

    ADS  CAS  PubMed  Google Scholar 

  10. 10.

    Hayashi-Nishino, M. et al. A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nat. Cell Biol. 11, 1433–1437 (2009).

    CAS  PubMed  Google Scholar 

  11. 11.

    Puri, C., Renna, M., Bento, C. F., Moreau, K. & Rubinsztein, D. C. Diverse autophagosome membrane sources coalesce in recycling endosomes. Cell 154, 1285–1299 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Ravikumar, B., Moreau, K., Jahreiss, L., Puri, C. & Rubinsztein, D. C. Plasma membrane contributes to the formation of pre-autophagosomal structures. Nat. Cell Biol. 12, 747–757 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Yla-Anttila, P., Vihinen, H., Jokitalo, E. & Eskelinen, E. L. 3D tomography reveals connections between the phagophore and endoplasmic reticulum. Autophagy 5, 1180–1185 (2009).

    PubMed  Google Scholar 

  14. 14.

    de la Ballina, L. R., Munson, M. J. & Simonsen, A. Lipids and lipid-binding proteins in selective autophagy. J. Mol. Biol. 432, 135–159 (2019).

  15. 15.

    Cornell, R. B. & Ridgway, N. D. CTP:phosphocholine cytidylyltransferase: function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis. Prog. Lipid Res. 59, 147–171 (2015).

    CAS  PubMed  Google Scholar 

  16. 16.

    Fagone, P. & Jackowski, S. Phosphatidylcholine and the CDP-choline cycle. Biochim. Biophys. Acta 1831, 523–532 (2013).

    CAS  PubMed  Google Scholar 

  17. 17.

    Nguyen, T. B. et al. DGAT1-dependent lipid droplet biogenesis protects mitochondrial function during starvation-induced autophagy. Dev. Cell 42, 9–21 (2017). e25.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Rambold, A. S., Cohen, S. & Lippincott-Schwartz, J. Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics. Dev. Cell 32, 678–692 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Jao, C. Y., Roth, M., Welti, R. & Salic, A. Metabolic labeling and direct imaging of choline phospholipids in vivo. Proc. Natl Acad. Sci. USA 106, 15332–15337 (2009).

    ADS  CAS  PubMed  Google Scholar 

  20. 20.

    Koyama-Honda, I., Itakura, E., Fujiwara, T. K. & Mizushima, N. Temporal analysis of recruitment of mammalian ATG proteins to the autophagosome formation site. Autophagy 9, 1491–1499 (2013).

    CAS  PubMed  Google Scholar 

  21. 21.

    Iyoshi, S. et al. Asymmetrical distribution of choline phospholipids revealed by click chemistry and freeze-fracture electron microscopy. ACS Chem. Biol. 9, 2217–2222 (2014).

    CAS  PubMed  Google Scholar 

  22. 22.

    Cheng, J. et al. Yeast and mammalian autophagosomes exhibit distinct phosphatidylinositol 3-phosphate asymmetries. Nat. Commun. 5, 3207 (2014).

    ADS  PubMed  Google Scholar 

  23. 23.

    Karim, M., Jackson, P. & Jackowski, S. Gene structure, expression and identification of a new CTP:phosphocholine cytidylyltransferase beta isoform. Biochim. Biophys. Acta 1633, 1–12 (2003).

    CAS  PubMed  Google Scholar 

  24. 24.

    Veitch, D. P., Gilham, D. & Cornell, R. B. The role of histidine residues in the HXGH site of CTP:phosphocholine cytidylyltransferase in CTP binding and catalysis. Eur. J. Biochem. 255, 227–234 (1998).

    CAS  PubMed  Google Scholar 

  25. 25.

    Helmink, B. A., Braker, J. D., Kent, C. & Friesen, J. A. Identification of lysine 122 and arginine 196 as important functional residues of rat CTP:phosphocholine cytidylyltransferase alpha. Biochemistry 42, 5043–5051 (2003).

    CAS  PubMed  Google Scholar 

  26. 26.

    Friesen, J. A., Campbell, H. A. & Kent, C. Enzymatic and cellular characterization of a catalytic fragment of CTP:phosphocholine cytidylyltransferase alpha. J. Biol. Chem. 274, 13384–13389 (1999).

    CAS  PubMed  Google Scholar 

  27. 27.

    Cao, J. et al. Targeting Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) with small molecule inhibitors for the treatment of metabolic diseases. J. Biol. Chem. 286, 41838–41851 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Llaverias, G., Laguna, J. C. & Alegret, M. Pharmacology of the ACAT inhibitor avasimibe (CI-1011). Cardiovasc Drug Rev. 21, 33–50 (2003).

    CAS  PubMed  Google Scholar 

  29. 29.

    Klionsky, D. J. et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12, 1–222 (2016).

    PubMed  PubMed Central  Google Scholar 

  30. 30.

    Mizushima, N., Yoshimori, T. & Levine, B. Methods in mammalian autophagy research. Cell 140, 313–326 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Gao, G., Sheng, Y., Yang, H., Chua, B. T. & Xu, L. DFCP1 associates with lipid droplets. Cell Biol. Int. 43, 1492–1504 (2019).

  32. 32.

    Li, D. et al. The ER-localized protein DFCP1 modulates ER-lipid droplet contact formation. Cell Rep. 27, 343–358 (2019). e345.

    CAS  PubMed  Google Scholar 

  33. 33.

    Poillet-Perez, L. & White, E. Role of tumor and host autophagy in cancer metabolism. Genes Dev. 33, 610–619 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Uemura, T. et al. A cluster of thin tubular structures mediates transformation of the endoplasmic reticulum to autophagic isolation membrane. Mol. Cell Biol. 34, 1695–1706 (2014).

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Schutter, M., Giavalisco, P., Brodesser, S. & Graef, M. Local fatty acid channeling into phospholipid synthesis drives phagophore expansion during autophagy. Cell 180, 135–149 (2020). e114.

    PubMed  Google Scholar 

  36. 36.

    Wang, L., Magdaleno, S., Tabas, I. & Jackowski, S. Early embryonic lethality in mice with targeted deletion of the CTP:phosphocholine cytidylyltransferase alpha gene (Pcyt1a). Mol. Cell Biol. 25, 3357–3363 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Jackowski, S. et al. Disruption of CCTbeta2 expression leads to gonadal dysfunction. Mol. Cell Biol. 24, 4720–4733 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Andrejeva, G. et al. De novo phosphatidylcholine synthesis is required for autophagosome membrane formation and maintenance during autophagy. Autophagy 16, 1044–1060 (2019).

  39. 39.

    Vance, D. E. & Ridgway, N. D. The methylation of phosphatidylethanolamine. Prog. Lipid Res. 27, 61–79 (1988).

    CAS  PubMed  Google Scholar 

  40. 40.

    Bae, E. J. et al. Phospholipase D1 regulates autophagic flux and clearance of alpha-synuclein aggregates. Cell Death Differ. 21, 1132–1141 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Dall’Armi, C. et al. The phospholipase D1 pathway modulates macroautophagy. Nat. Commun. 1, 142 (2010).

    ADS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Holland, P. et al. HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels. Nat. Commun. 7, 13889 (2016).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Moreau, K., Ravikumar, B., Puri, C. & Rubinsztein, D. C. Arf6 promotes autophagosome formation via effects on phosphatidylinositol 4,5-bisphosphate and phospholipase D. J. Cell Biol. 196, 483–496 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Jang, Y. H., Choi, K. Y. & Min, D. S. Phospholipase D-mediated autophagic regulation is a potential target for cancer therapy. Cell Death Differ. 21, 533–546 (2014).

    CAS  PubMed  Google Scholar 

  45. 45.

    Dupont, N. et al. Neutral lipid stores and lipase PNPLA5 contribute to autophagosome biogenesis. Curr. Biol. 24, 609–620 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Shpilka, T. et al. Lipid droplets and their component triglycerides and steryl esters regulate autophagosome biogenesis. EMBO J. 34, 2117–2131 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    English, A. R. & Voeltz, G. K. Rab10 GTPase regulates ER dynamics and morphology. Nat. Cell Biol. 15, 169–178 (2013).

    CAS  PubMed  Google Scholar 

  48. 48.

    Nishimura, T. et al. Autophagosome formation is initiated at phosphatidylinositol synthase-enriched ER subdomains. EMBO J. 36, 1719–1735 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Karanasios, E. et al. Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles. Nat. Commun. 7, 12420 (2016).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Orsi, A. et al. Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy. Mol. Biol. Cell 23, 1860–1873 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Singh, R. et al. Autophagy regulates lipid metabolism. Nature 458, 1131–1135 (2009).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Li, D. et al. Storage lipid synthesis is necessary for autophagy induced by nitrogen starvation. FEBS Lett. 589, 269–276 (2015).

    CAS  PubMed  Google Scholar 

  53. 53.

    Velazquez, A. P., Tatsuta, T., Ghillebert, R., Drescher, I. & Graef, M. Lipid droplet-mediated ER homeostasis regulates autophagy and cell survival during starvation. J. Cell Biol. 212, 621–631 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Ogasawara, Y., Tsuji, T. & Fujimoto, T. Multifarious roles of lipid droplets in autophagy—target, product, and what else? Semin. Cell Dev. Biol. https://doi.org/10.1016/j.semcdb.2020.02.013 (2020).

  55. 55.

    Kimmelman, A. C. & White, E. Autophagy and tumor metabolism. Cell Metab. 25, 1037–1043 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Liu, E. Y. & Ryan, K. M. Autophagy and cancer–issues we need to digest. J. Cell Sci. 125, 2349–2358 (2012).

    PubMed  Google Scholar 

  57. 57.

    Koizume, S. & Miyagi, Y. Lipid droplets: a key cellular organelle associated with cancer cell survival under normoxia and hypoxia. Int. J. Mol. Sci. 17, 1430 (2016).

  58. 58.

    Glunde, K., Bhujwalla, Z. M. & Ronen, S. M. Choline metabolism in malignant transformation. Nat. Rev. Cancer 11, 835–848 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Levy, J. M. M., Towers, C. G. & Thorburn, A. Targeting autophagy in cancer. Nat. Rev. Cancer 17, 528–542 (2017).

    CAS  PubMed  Google Scholar 

  60. 60.

    Brasaemle, D. L., Barber, T., Kimmel, A. R. & Londos, C. Post-translational regulation of perilipin expression. Stabilization by stored intracellular neutral lipids. J. Biol. Chem. 272, 9378–9387 (1997).

    CAS  PubMed  Google Scholar 

  61. 61.

    Lykidis, A., Baburina, I. & Jackowski, S. Distribution of CTP:phosphocholine cytidylyltransferase (CCT) isoforms. Identification of a new CCTbeta splice variant. J. Biol. Chem. 274, 26992–27001 (1999).

    CAS  PubMed  Google Scholar 

  62. 62.

    Stephens, D. J., Lin-Marq, N., Pagano, A., Pepperkok, R. & Paccaud, J. P. COPI-coated ER-to-Golgi transport complexes segregate from COPII in close proximity to ER exit sites. J. Cell Sci. 113, 2177–2185 (2000).

    CAS  PubMed  Google Scholar 

  63. 63.

    Morita, S., Kojima, T. & Kitamura, T. Plat-E: an efficient and stable system for transient packaging of retroviruses. Gene Ther. 7, 1063–1066 (2000).

    CAS  PubMed  Google Scholar 

  64. 64.

    Kitamura, T. et al. Retrovirus-mediated gene transfer and expression cloning: powerful tools in functional genomics. Exp. Hematol. 31, 1007–1014 (2003).

    CAS  PubMed  Google Scholar 

  65. 65.

    Longo, P. A., Kavran, J. M., Kim, M. S. & Leahy, D. J. Transient mammalian cell transfection with polyethylenimine (PEI). Methods Enzymol. 529, 227–240 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66.

    Ran, F. A. et al. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8, 2281–2308 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Naito, Y., Hino, K., Bono, H. & Ui-Tei, K. CRISPRdirect: software for designing CRISPR/Cas guide RNA with reduced off-target sites. Bioinformatics 31, 1120–1123 (2015).

    CAS  PubMed  Google Scholar 

  68. 68.

    Yu, W., Cassara, J. & Weller, P. F. Phosphatidylinositide 3-kinase localizes to cytoplasmic lipid bodies in human polymorphonuclear leukocytes and other myeloid-derived cells. Blood 95, 1078–1085 (2000).

    CAS  PubMed  Google Scholar 

  69. 69.

    Vassar, V., Hagen, C., Ludwig, J., Thomas, R. & Zhou, J. One-step method of phosphatidylcholine extraction and separation. Biotechniques 42, 444 (2007).

    Google Scholar 

  70. 70.

    Folch, J., Lees, M. & Sloane Stanley, G. H. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226, 497–509 (1957).

    CAS  PubMed  Google Scholar 

  71. 71.

    White, D. L., Mazurkiewicz, J. E. & Barrnett, R. J. A chemical mechanism for tissue staining by osmium tetroxide-ferrocyanide mixtures. J. Histochem. Cytochem. 27, 1084–1091 (1979).

    CAS  PubMed  Google Scholar 

  72. 72.

    Hirsch, J. G., Fedorko, M. E. & Cohn, Z. A. Vesicle fusion and formation at the surface of pinocytic vacuoles in macrophages. J. Cell Biol. 38, 629–632 (1968).

    CAS  PubMed  PubMed Central  Google Scholar 

Original Text (This is the original text for your reference.)

  1. 1.

    Mizushima, N., Yoshimori, T. & Ohsumi, Y. The role of Atg proteins in autophagosome formation. Annu. Rev. Cell Dev. Biol. 27, 107–132 (2011).

    CAS  PubMed  Google Scholar 

  2. 2.

    Bento, C. F. et al. Mammalian autophagy: How does it work? Annu. Rev. Biochem. 85, 685–713 (2016).

    CAS  PubMed  Google Scholar 

  3. 3.

    Dikic, I. & Elazar, Z. Mechanism and medical implications of mammalian autophagy. Nat. Rev. Mol. Cell Biol. 19, 349–364 (2018).

    CAS  PubMed  Google Scholar 

  4. 4.

    Hurley, J. H. & Young, L. N. Mechanisms of autophagy initiation. Annu. Rev. Biochem. 86, 225–244 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Nakatogawa, H. Mechanisms governing autophagosome biogenesis. Nat. Rev. Mol. Cell Biol. 21, 439–458 (2020).

  6. 6.

    Axe, E. L. et al. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J. Cell Biol. 182, 685–701 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Ge, L., Melville, D., Zhang, M. & Schekman, R. The ER-Golgi intermediate compartment is a key membrane source for the LC3 lipidation step of autophagosome biogenesis. Elife 2, e00947 (2013).

    PubMed  PubMed Central  Google Scholar 

  8. 8.

    Hailey, D. W. et al. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 141, 656–667 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Hamasaki, M. et al. Autophagosomes form at ER-mitochondria contact sites. Nature 495, 389–393 (2013).

    ADS  CAS  PubMed  Google Scholar 

  10. 10.

    Hayashi-Nishino, M. et al. A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nat. Cell Biol. 11, 1433–1437 (2009).

    CAS  PubMed  Google Scholar 

  11. 11.

    Puri, C., Renna, M., Bento, C. F., Moreau, K. & Rubinsztein, D. C. Diverse autophagosome membrane sources coalesce in recycling endosomes. Cell 154, 1285–1299 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Ravikumar, B., Moreau, K., Jahreiss, L., Puri, C. & Rubinsztein, D. C. Plasma membrane contributes to the formation of pre-autophagosomal structures. Nat. Cell Biol. 12, 747–757 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Yla-Anttila, P., Vihinen, H., Jokitalo, E. & Eskelinen, E. L. 3D tomography reveals connections between the phagophore and endoplasmic reticulum. Autophagy 5, 1180–1185 (2009).

    PubMed  Google Scholar 

  14. 14.

    de la Ballina, L. R., Munson, M. J. & Simonsen, A. Lipids and lipid-binding proteins in selective autophagy. J. Mol. Biol. 432, 135–159 (2019).

  15. 15.

    Cornell, R. B. & Ridgway, N. D. CTP:phosphocholine cytidylyltransferase: function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis. Prog. Lipid Res. 59, 147–171 (2015).

    CAS  PubMed  Google Scholar 

  16. 16.

    Fagone, P. & Jackowski, S. Phosphatidylcholine and the CDP-choline cycle. Biochim. Biophys. Acta 1831, 523–532 (2013).

    CAS  PubMed  Google Scholar 

  17. 17.

    Nguyen, T. B. et al. DGAT1-dependent lipid droplet biogenesis protects mitochondrial function during starvation-induced autophagy. Dev. Cell 42, 9–21 (2017). e25.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Rambold, A. S., Cohen, S. & Lippincott-Schwartz, J. Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics. Dev. Cell 32, 678–692 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Jao, C. Y., Roth, M., Welti, R. & Salic, A. Metabolic labeling and direct imaging of choline phospholipids in vivo. Proc. Natl Acad. Sci. USA 106, 15332–15337 (2009).

    ADS  CAS  PubMed  Google Scholar 

  20. 20.

    Koyama-Honda, I., Itakura, E., Fujiwara, T. K. & Mizushima, N. Temporal analysis of recruitment of mammalian ATG proteins to the autophagosome formation site. Autophagy 9, 1491–1499 (2013).

    CAS  PubMed  Google Scholar 

  21. 21.

    Iyoshi, S. et al. Asymmetrical distribution of choline phospholipids revealed by click chemistry and freeze-fracture electron microscopy. ACS Chem. Biol. 9, 2217–2222 (2014).

    CAS  PubMed  Google Scholar 

  22. 22.

    Cheng, J. et al. Yeast and mammalian autophagosomes exhibit distinct phosphatidylinositol 3-phosphate asymmetries. Nat. Commun. 5, 3207 (2014).

    ADS  PubMed  Google Scholar 

  23. 23.

    Karim, M., Jackson, P. & Jackowski, S. Gene structure, expression and identification of a new CTP:phosphocholine cytidylyltransferase beta isoform. Biochim. Biophys. Acta 1633, 1–12 (2003).

    CAS  PubMed  Google Scholar 

  24. 24.

    Veitch, D. P., Gilham, D. & Cornell, R. B. The role of histidine residues in the HXGH site of CTP:phosphocholine cytidylyltransferase in CTP binding and catalysis. Eur. J. Biochem. 255, 227–234 (1998).

    CAS  PubMed  Google Scholar 

  25. 25.

    Helmink, B. A., Braker, J. D., Kent, C. & Friesen, J. A. Identification of lysine 122 and arginine 196 as important functional residues of rat CTP:phosphocholine cytidylyltransferase alpha. Biochemistry 42, 5043–5051 (2003).

    CAS  PubMed  Google Scholar 

  26. 26.

    Friesen, J. A., Campbell, H. A. & Kent, C. Enzymatic and cellular characterization of a catalytic fragment of CTP:phosphocholine cytidylyltransferase alpha. J. Biol. Chem. 274, 13384–13389 (1999).

    CAS  PubMed  Google Scholar 

  27. 27.

    Cao, J. et al. Targeting Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) with small molecule inhibitors for the treatment of metabolic diseases. J. Biol. Chem. 286, 41838–41851 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Llaverias, G., Laguna, J. C. & Alegret, M. Pharmacology of the ACAT inhibitor avasimibe (CI-1011). Cardiovasc Drug Rev. 21, 33–50 (2003).

    CAS  PubMed  Google Scholar 

  29. 29.

    Klionsky, D. J. et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12, 1–222 (2016).

    PubMed  PubMed Central  Google Scholar 

  30. 30.

    Mizushima, N., Yoshimori, T. & Levine, B. Methods in mammalian autophagy research. Cell 140, 313–326 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Gao, G., Sheng, Y., Yang, H., Chua, B. T. & Xu, L. DFCP1 associates with lipid droplets. Cell Biol. Int. 43, 1492–1504 (2019).

  32. 32.

    Li, D. et al. The ER-localized protein DFCP1 modulates ER-lipid droplet contact formation. Cell Rep. 27, 343–358 (2019). e345.

    CAS  PubMed  Google Scholar 

  33. 33.

    Poillet-Perez, L. & White, E. Role of tumor and host autophagy in cancer metabolism. Genes Dev. 33, 610–619 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Uemura, T. et al. A cluster of thin tubular structures mediates transformation of the endoplasmic reticulum to autophagic isolation membrane. Mol. Cell Biol. 34, 1695–1706 (2014).

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Schutter, M., Giavalisco, P., Brodesser, S. & Graef, M. Local fatty acid channeling into phospholipid synthesis drives phagophore expansion during autophagy. Cell 180, 135–149 (2020). e114.

    PubMed  Google Scholar 

  36. 36.

    Wang, L., Magdaleno, S., Tabas, I. & Jackowski, S. Early embryonic lethality in mice with targeted deletion of the CTP:phosphocholine cytidylyltransferase alpha gene (Pcyt1a). Mol. Cell Biol. 25, 3357–3363 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Jackowski, S. et al. Disruption of CCTbeta2 expression leads to gonadal dysfunction. Mol. Cell Biol. 24, 4720–4733 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Andrejeva, G. et al. De novo phosphatidylcholine synthesis is required for autophagosome membrane formation and maintenance during autophagy. Autophagy 16, 1044–1060 (2019).

  39. 39.

    Vance, D. E. & Ridgway, N. D. The methylation of phosphatidylethanolamine. Prog. Lipid Res. 27, 61–79 (1988).

    CAS  PubMed  Google Scholar 

  40. 40.

    Bae, E. J. et al. Phospholipase D1 regulates autophagic flux and clearance of alpha-synuclein aggregates. Cell Death Differ. 21, 1132–1141 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Dall’Armi, C. et al. The phospholipase D1 pathway modulates macroautophagy. Nat. Commun. 1, 142 (2010).

    ADS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Holland, P. et al. HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels. Nat. Commun. 7, 13889 (2016).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Moreau, K., Ravikumar, B., Puri, C. & Rubinsztein, D. C. Arf6 promotes autophagosome formation via effects on phosphatidylinositol 4,5-bisphosphate and phospholipase D. J. Cell Biol. 196, 483–496 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Jang, Y. H., Choi, K. Y. & Min, D. S. Phospholipase D-mediated autophagic regulation is a potential target for cancer therapy. Cell Death Differ. 21, 533–546 (2014).

    CAS  PubMed  Google Scholar 

  45. 45.

    Dupont, N. et al. Neutral lipid stores and lipase PNPLA5 contribute to autophagosome biogenesis. Curr. Biol. 24, 609–620 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Shpilka, T. et al. Lipid droplets and their component triglycerides and steryl esters regulate autophagosome biogenesis. EMBO J. 34, 2117–2131 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    English, A. R. & Voeltz, G. K. Rab10 GTPase regulates ER dynamics and morphology. Nat. Cell Biol. 15, 169–178 (2013).

    CAS  PubMed  Google Scholar 

  48. 48.

    Nishimura, T. et al. Autophagosome formation is initiated at phosphatidylinositol synthase-enriched ER subdomains. EMBO J. 36, 1719–1735 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Karanasios, E. et al. Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles. Nat. Commun. 7, 12420 (2016).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Orsi, A. et al. Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy. Mol. Biol. Cell 23, 1860–1873 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Singh, R. et al. Autophagy regulates lipid metabolism. Nature 458, 1131–1135 (2009).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Li, D. et al. Storage lipid synthesis is necessary for autophagy induced by nitrogen starvation. FEBS Lett. 589, 269–276 (2015).

    CAS  PubMed  Google Scholar 

  53. 53.

    Velazquez, A. P., Tatsuta, T., Ghillebert, R., Drescher, I. & Graef, M. Lipid droplet-mediated ER homeostasis regulates autophagy and cell survival during starvation. J. Cell Biol. 212, 621–631 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Ogasawara, Y., Tsuji, T. & Fujimoto, T. Multifarious roles of lipid droplets in autophagy—target, product, and what else? Semin. Cell Dev. Biol. https://doi.org/10.1016/j.semcdb.2020.02.013 (2020).

  55. 55.

    Kimmelman, A. C. & White, E. Autophagy and tumor metabolism. Cell Metab. 25, 1037–1043 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Liu, E. Y. & Ryan, K. M. Autophagy and cancer–issues we need to digest. J. Cell Sci. 125, 2349–2358 (2012).

    PubMed  Google Scholar 

  57. 57.

    Koizume, S. & Miyagi, Y. Lipid droplets: a key cellular organelle associated with cancer cell survival under normoxia and hypoxia. Int. J. Mol. Sci. 17, 1430 (2016).

  58. 58.

    Glunde, K., Bhujwalla, Z. M. & Ronen, S. M. Choline metabolism in malignant transformation. Nat. Rev. Cancer 11, 835–848 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Levy, J. M. M., Towers, C. G. & Thorburn, A. Targeting autophagy in cancer. Nat. Rev. Cancer 17, 528–542 (2017).

    CAS  PubMed  Google Scholar 

  60. 60.

    Brasaemle, D. L., Barber, T., Kimmel, A. R. & Londos, C. Post-translational regulation of perilipin expression. Stabilization by stored intracellular neutral lipids. J. Biol. Chem. 272, 9378–9387 (1997).

    CAS  PubMed  Google Scholar 

  61. 61.

    Lykidis, A., Baburina, I. & Jackowski, S. Distribution of CTP:phosphocholine cytidylyltransferase (CCT) isoforms. Identification of a new CCTbeta splice variant. J. Biol. Chem. 274, 26992–27001 (1999).

    CAS  PubMed  Google Scholar 

  62. 62.

    Stephens, D. J., Lin-Marq, N., Pagano, A., Pepperkok, R. & Paccaud, J. P. COPI-coated ER-to-Golgi transport complexes segregate from COPII in close proximity to ER exit sites. J. Cell Sci. 113, 2177–2185 (2000).

    CAS  PubMed  Google Scholar 

  63. 63.

    Morita, S., Kojima, T. & Kitamura, T. Plat-E: an efficient and stable system for transient packaging of retroviruses. Gene Ther. 7, 1063–1066 (2000).

    CAS  PubMed  Google Scholar 

  64. 64.

    Kitamura, T. et al. Retrovirus-mediated gene transfer and expression cloning: powerful tools in functional genomics. Exp. Hematol. 31, 1007–1014 (2003).

    CAS  PubMed  Google Scholar 

  65. 65.

    Longo, P. A., Kavran, J. M., Kim, M. S. & Leahy, D. J. Transient mammalian cell transfection with polyethylenimine (PEI). Methods Enzymol. 529, 227–240 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66.

    Ran, F. A. et al. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8, 2281–2308 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Naito, Y., Hino, K., Bono, H. & Ui-Tei, K. CRISPRdirect: software for designing CRISPR/Cas guide RNA with reduced off-target sites. Bioinformatics 31, 1120–1123 (2015).

    CAS  PubMed  Google Scholar 

  68. 68.

    Yu, W., Cassara, J. & Weller, P. F. Phosphatidylinositide 3-kinase localizes to cytoplasmic lipid bodies in human polymorphonuclear leukocytes and other myeloid-derived cells. Blood 95, 1078–1085 (2000).

    CAS  PubMed  Google Scholar 

  69. 69.

    Vassar, V., Hagen, C., Ludwig, J., Thomas, R. & Zhou, J. One-step method of phosphatidylcholine extraction and separation. Biotechniques 42, 444 (2007).

    Google Scholar 

  70. 70.

    Folch, J., Lees, M. & Sloane Stanley, G. H. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226, 497–509 (1957).

    CAS  PubMed  Google Scholar 

  71. 71.

    White, D. L., Mazurkiewicz, J. E. & Barrnett, R. J. A chemical mechanism for tissue staining by osmium tetroxide-ferrocyanide mixtures. J. Histochem. Cytochem. 27, 1084–1091 (1979).

    CAS  PubMed  Google Scholar 

  72. 72.

    Hirsch, J. G., Fedorko, M. E. & Cohn, Z. A. Vesicle fusion and formation at the surface of pinocytic vacuoles in macrophages. J. Cell Biol. 38, 629–632 (1968).

    CAS  PubMed  PubMed Central  Google Scholar 

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