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Publications (2)19.48 Total impact

  • Martina Wirth, Justin Joachim, Sharon A Tooze
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    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.
    Seminars in Cancer Biology 05/2013; · 7.44 Impact Factor
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    ABSTRACT: Autophagy is a conserved and highly regulated catabolic pathway, transferring cytoplasmic components in autophagosomes to lysosomes for degradation and providing amino acids during starvation. In multicellular organisms autophagy plays an important role for tissue homeostasis, and deregulation of autophagy has been implicated in a broad range of diseases, including cancer and neurodegenerative disorders. In mammals, many aspects of autophagy still need to be fully elucidated: what is the exact hierarchy and relationship between ATG proteins and other factors that lead to the formation and expansion of phagophores? Where does the membrane source for autophagosome formation originate? Which signaling events trigger amino acid starvation-induced autophagy? How are the activities of ULK1/2 and the class III PtdIns3K regulated and linked to each other? To develop therapeutic strategies to manipulate autophagy in human disease, a comprehensive understanding of the molecular protein machinery mediating and regulating autophagy is required.
    Autophagy 09/2012; 8(9):1397-400. · 12.04 Impact Factor