Chapter 23 - Autophagy Regulates Control of Intracellular Energy Stores

Abstract

During periods of nutrient deficit, cells initiate recycling programs to break down complex intracellular components within lysosomes, enabling them to reutilize the carbon backbone of macromolecules for the subsequent generation of energy. This recycling system is called the “self (auto) eating (phagy)” autophagy program. Multiple components of the cell (macroautophagy or autophagy), distinct portions of the cytoplasm (microautophagy), protein aggregates (chaperone-mediated autophagy), impaired organelles such as mitochondria (mitophagy) or metabolic stores including lipid droplets (lipophagy) and glycogen (glycophagy) can be recycled through various regulated autophagy programs. Over the last decade the molecular machinery orchestrating the various autophagy programs has been delineated. Fasting has been employed as a trigger to initiate these programs, and nutrient-sensing pathways including AMPK and sirtuins have been identified as important apical autophagy signaling mediators. Adaptive autophagy programs sustain energy homeostasis, whereas incessant or perturbed autophagy can be associated with pathology. On the opposite side of this spectrum, caloric excess has been found to disrupt autophagy programs and that these perturbations may also play a role in nutrient excess pathophysiology. Together, these findings support that this nutrient-sensing recycling system may be central to the maintenance of cellular homeostasis. At the same time emerging data shows that autophagy also plays an integral role in sustaining intracellular quality control by removal of damaged components/organelles within cells. This chapter will give an overview of the nutrient-sensing role in the regulation of autophagy programs and, where known how these modulations affect cardiometabolic disease.