2013 Nobel Prize Winner will speak on "Biogenesis and Function of the Autophagosome"

The NIH Cell Biology and Metabolism Program will host Randy Schekman, co-winner of the 2013 Nobel Prize for Physiology or Medicine. The pathway of autophagy has assumed an important position in the analysis of mammalian cellular response to stress, hypoxia and pathogen infection. Autophagosomes mature by growth and envelopment of cytosolic proteins and organelles that are trapped within the inner membrane of a two-membrane organelle. Trapped proteins are delivered by autophagosome fusion to the lysosome where protein and polysaccharide degradation permit amino acids and sugars to be recycled. A pre-autophagsosomal membrane matures by the addition of membrane material from various intracellular sources and the attachment of peripheral proteins that remain bound through a covalent lipidation reaction. The origin and the mechanism of generation of the pre-autophagic membrane are poorly understood. Published evidence suggests an origin of this membrane on the ER, on the mitochondrial surface or possibly the Golgi or plasma membrane. We have addressed these issues with the development and analysis of a cell-free reaction that reproduces the lipidation of a major peripheral autophagosomal protein, LC3. Mouse embryonic fibroblasts (MEFs) taken from a mouse strain deficient in Atg5 are unable to lipidate LC3 and other targets of lipidation involved in the autophagic process. A crude membrane fraction isolated from these MEFs was mixed with cytosol harvested from normal cells t...
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