Introduction to Autophagy.
1. Autophagy is a lysosomal degradation pathway that is essential for survival, differentiation, development, and homeostasis. Autophagy principally serves an adaptive role to protect organisms against diverse pathologies, including infections, cancer, neurodegeneration, aging, and heart disease. However, in certain experimental disease settings, the self-cannibalistic or, paradoxically, even the prosurvival functions of autophagy may be deleterious.
[4. Beth Levine et al., Autophagy in the Pathogenesis of Disease, Cell, 132, Issue 1, 27-42, 2008]
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| The Autophagic Pathway |
2. Autophagy (Beth Levine: HHMI) is an evolutionarily conserved pathway that involves the lysosomal degradation of long-lived cellular proteins and organelles. Our laboratory identified the first mammalian autophagy protein, Beclin 1, in a screen for novel proteins that interact with the apoptosis inhibitor, Bcl-2. Work by our laboratory and others has established that autophagy participates in a number of fundamental biological processes and diseases. Using genetic approaches in different model organisms, we have shown that beclin 1 and autophagy function in tumor suppression, in development and lifespan extension, and in innate antiviral immunity. We have also found that the Bcl-2/Beclin 1 complex provides rheostatic control on autophagy and cell death. Our ongoing research aims to further identify the precise role of autophagy in antimicrobial host defense, in cancer biology, in cell death regulation, and in the prevention of aging and neurodegenerative diseases. To accomplish this goal, we are using a combination of biochemistry, structural biology, molecular biology, and genetic approaches in yeast, C. elegans, and mammalian systems.
3. Autophagy is the major cellular pathway for the degradation of long-lived proteins and cytoplasmic organelles. It involves the rearrangement of subcellular membranes to sequester cargo for delivery to the lysosome where the sequestered material is degraded and recycled. For many decades, it has been known that autophagy occurs in a wide range of eukaryotic organisms and in multiple different cell types during starvation, cellular and tissue remodeling, and cell death. However, until recently, the biological functions of autophagy have been largely unknown. The identification of a set of evolutionarily conserved genes that are essential for autophagy has opened up new frontiers for understanding the role of autophagy in diverse biological processes.
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