Abstract: Series 99, Lecture 3

The Harvey Lectures Series 99 (2003—2004)

previous lecture | next lecture

Lecture #3: Thursday, January 15, 2004 — Time and Location

Autophagy in Development, Tumor Suppression and Innate Immunity

Beth Levine, MD

Associate Professor of Medicine

College of Physicians and Surgeons, Columbia University

New York, New York

Autophagy is the major cellular pathway for degrading longlived proteins and cytoplasmic organelles. It involves the rearrangement of subcellular membranes to sequester cytoplasm and organelles for delivery to the lysosome where the sequestered cargo 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 functions that autophagy may play in normal biology and in disease were not understood. The identification of a set of evolutionarily conserved genes that are essential for autophagy has opened up new frontiers for deciphering the role of autophagy in diverse biological processes. Following our identification of beclin 1 as the first mammalian autophagy gene, we have used genetic approaches to show an essential role for autophagy genes in dauer development and lifespan extension in C. elegans, in mouse embryonic development and tumor suppression, and in innate immunity against intracellular pathogens. The evidence for these findings will be presented and the broader implications of our work for understanding the role of autophagy in normal biology and in disease pathogenesis will be discussed.