Autophagy, cell death and disease

Autophagy is characterized by sequestration of bulk cytoplasm and organelles in double or multimembrane autophagic vesicles, and their delivery to and subsequent degradation by the cell's own lysosomal system. This cellular phenomenon has multiple physiological functions including protein degradation and organelle turnover. Increasing lines of evidence indicate that autophagy machinery may be recruited by an alternative, caspase-independent and non-apoptotic form of programmed cell death named "autophagic cell death". In some settings autophagy and apoptosis seem to be interconnected positively or negatively, introducing the concept of "molecular switches" or "integration points" between them. Consequently, autophagy abnormalities are frequent in various human diseases including cancer. Therefore, understanding the molecular mechanisms regulating human autophagy is crucial for the development of new approaches to diagnose and treat major health problems. In our lab in Sabanci University, Istanbul, we performed several unbiased screens to identify new regulators of human autophagy. Several new proteins, molecules and pathways were discovered and analyzed functionally. Consequences of autophagy abnormalities in human disease and potential of drug-mediated autophagy modulation in disease treatment will be discussed from a basic and clinical scientific point of view.