Putting the brakes on autophagy: The role of heparan sulfate modified proteins in the balance of anabolic and catabolic pathways and intracellular quality control

Autophagy is a fundamental cellular process discovered as a response to nutrient deprivation. It provides the cellular and molecular machinery for catabolism of cellular constituents, generating energy and providing building blocks for continued survival. However, autophagy does much more than provide an entry into catabolic pathways, it provides a mechanism for intracellular quality control, removing damaged organelles and misfolded proteins, processes critical for cellular health. Autophagy serves as a counterpoint to cell growth and anabolic events, activated when growth is not possible or is suppressed. Hence, there is an inherent antagonism between autophagy and growth. Heparan sulfate modified proteins are important co-receptors that generally promote growth factor activity and are therefore positioned within signaling networks that inhibit, or negatively regulate autophagy levels. This review summarizes evidence that heparan sulfate modified proteins provide an evolutionarily conserved inhibitory modulation of autophagy that can have profound effects on cell physiology and organismal responses to stress.