Autophagy in Nonmammalian Systems

Abstract

Autophagy, or ‘self‐eating’, is a catabolic process that enables lysosome‐mediated degradation of cytoplasmic contents and recycling of macromolecules to be used in essential cellular processes. This process enables cells to survive during nutrient restriction, participates in cell death during development and functions in clearance of protein aggregates and intracellular pathogens. Autophagy has been widely studied in yeast, Drosophila and Caenorhabditis elegans , and studies in these organisms have revealed regulation by multiple cellular pathways. These include cell growth regulators, such as the Class I PI3 kinase and target of rapamycin (Tor), as well as cell death regulators, including caspases. Defects in autophagy are associated with neurodegeneration, pathogen infection, cancer and reduced lifespan. Genetic experiments in model organisms have been critical in determining how autophagy functions in health and disease. Key Concepts Over 30 atg genes have been shown to regulate autophagy. Autophagy is induced in response to starvation and oxidative stress, enabling cells to recycle macromolecules and degrade damaged organelles. Autophagy is required for steroid‐triggered removal of larval tissues during Drosophila melanogaster development. Autophagosomes can sequester intracellular pathogens, which evade the cell's phagocytic machinery and traffic them to the lysosome for degradation. Decreased autophagy leads to an inability to clear protein aggregates and mutant polyglutamine containing proteins from neurons in fly and worm neurodegeneration models. Induction of autophagy in flies and worms can extend lifespan, whereas its block leads to increased neuronal cell death and reduced lifespan. Autophagy has a context‐dependent role in tumourigenesis.