Autophagy in cellular metabolism and cancer

Abstract

Autophagy is a catabolic process mediated by incorporation of cellular material into cytosolic membrane vesicles for lysosomal degradation. It is crucial for maintaining cell viability and homeostasis in response to numerous stressful conditions. In this Review, the role of autophagy in both normal biology and disease is discussed. Emphasis is given to the interplay of autophagy with nutrient signaling through the ULK1 autophagy pre-initiation complex. Furthermore, related cellular processes utilizing components of the canonical autophagy pathway are discussed due to their potential roles in nutrient scavenging. Finally, the role of autophagy in cancer and its potential as a cancer therapeutic target are considered.

Figure 3. LC3 lipidation in non-autophagic processes.

The phagocytosis of apoptotic bodies and macropinocytic uptake of serum albumin are shown as examples of extracellular substrates that may be degraded in an autophagy protein–dependent manner. Shaded box at the right lists multiple non-autophagic processes utilizing LC3 lipidation, as well as their cargos and biological functions. Their potential common roles in nutrient scavenging are emphasized.

Figure 2. The autophagy pathway senses various nutrient signals via the ULK1 complex.

Multiple nutrient-sensing mechanisms, including that modulated by mTORC1, AMPK, and acetyl-CoA, can directly interact with the ULK1 complex and thus regulate autophagy. Autophagy, by recycling amino acids to the cytoplasm, can reactivate mTORC1, and thus feedback suppress the autophagy function of the ULK1 complex. Pi, phosphorylation; Ac, acetylation; ATG16, ATG16L1. The dual-direction arrow indicates protein-protein interaction.

Figure 1. The autophagy pathway and its role in biology and diseases.

Schematic of the intracellular membrane events involved in the autophagy pathway. Shaded box at the right side lists examples of biological functions that autophagy can accomplish by targeting specific cargos, as well as diseases linked to the deficiency of these autophagy functions. Text at the bottom right describes roles of autophagy-mediated nutrient recycling.