Autophagy

By Yoskaly Lazo-Fernandez, PhD

By Christina Towers, PhD

By Yoskaly Lazo-Fernandez, PhD

By Christina Towers, PhD

By Christina Towers, PhD

By Christina Towers, PhD

Autophagy is an essential process that cells utilize to degrade and recycle damaged material and fuel metabolism, especially under stress.  The process is evolutionarily conserved and complex, relying on over 20 key proteins. Induction of autophagy is mediated by the formation of the ULK and BECLIN complexes, the latter of which includes BH3-containing proteins and AMBRA1, resulting in the formation of a double membrane phagophore structure.

Hypoxia is a common feature of most tumors and is a product of rapid cell growth and poor vascularization¹. When oxygen availability is low in the tumor environment, the hypoxia inducing transcription factors (HIFs) regulate a variety of signaling programs that can affect the balance between tumor cell apoptosis² and autophagy³.  In normoxia, HIFs are bound by the von Hippel-Lindau protein (VHL) in the cytosol where it is degraded by the proteasome, however, under hypoxia HIFs are translocated to the nucleus where they activate survival signals.

Autophagy more than a cytosolic event

Autophagy is a cellular process whereby cytosolic components are broken down and eliminated or recycled. As a homeostatic mechanism, basal autophagic activity eliminates excess or abnormal proteins and organelles1. As an induced process, autophagy may be triggered by various external challenges, such as decreased nutrient and energy resources, and oxidative stress¹.

Cell death/recycling pathways such as apoptosis, necroptosis, and autophagy are an integral part of the growth, development, homeostasis as well as the pathophysiology in the life of living organisms. These signaling pathways are highly regulated and some of their key regulatory targets are discussed below.

Apoptosis

Apoptosis, programmed cell death, is primarily characterized by the activation of caspases which further regulate the mass cleavage of proteins and DNA. Some of major the proteins responsible for various apoptotic events are: