Cell death and autophagy: a historical perspective

Abstract

The term "autophagy" defines an evolutionarily conserved mechanism by which eukaryotic cells recycle or degrade internal constituents in a membrane-trafficking pathway. Thus, autophagy helps providing the cells with a constant supply of biomolecules and energy for maintenance of homeostasis under stressful conditions. From this point of view autophagy seems to come into play as a survival mechanism. However, accumulating evidence also suggests that autophagy may contribute to cellular demise, and intricate connections between autophagy and cell death were reported. Autophagy dysregulations were observed in a wide spectrum of diseases, including cancer, neurodegenerative diseases, metabolic diseases and infections. Therefore, how autophagy contributes to cell death, and how autophagy-related cell death switches are controlled are important issues to be addressed from both a basic scientific and a clinical point of view. In this chapter, we summarized the history of authophagy and its relation to cell death, and discussed the evolution of the much debated “autophagic cell death” concept.