Autophagosome formation—The role of ULK1 and Beclin1–PI3KC3 complexes in setting the stage

• Published in: Seminars in cancer biology Vol. 23; no. 5; pp. 301 - 309
• Main Authors: Wirth, Martina, Joachim, Justin, Tooze, Sharon A
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-10-2013
• Subjects: Animals; Autophagy; Autophagy - physiology; Beclin1; Hematology, Oncology and Palliative Medicine; Humans; Membrane Proteins - metabolism; Phagosomes - physiology; Phosphatidylinositol 3-Kinases - metabolism; Post-translational modifications; Protein Interaction Maps; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases - metabolism; Signal Transduction; ULK1; ULK1; Beclin1; Post-translational modifications; Autophagy
• ISSN: 1044-579X; 1096-3650
• DOI: 10.1016/j.semcancer.2013.05.007

Abstract Autophagy is a conserved and highly regulated degradative membrane trafficking pathway, maintaining energy homeostasis and protein synthesis during nutrient stress. Our understanding of how the autophagy machinery is regulated has expanded greatly over recent years. The ULK and Beclin1–PI3KC3 complexes are key signaling complexes required for autophagosome formation. The nutrient and energy sensors mTORC1 and AMPK signal directly to the ULK complex and affect its activity. Formation and activation of distinct Beclin1–PI3KC3 complexes produces PI3P, a signaling lipid required for the recruitment of autophagy effectors. In this review we discuss how the mammalian ULK1 and Beclin1 complexes are controlled by post-translational modifications and protein–protein interactions and we highlight data linking these complexes together.