Autophagi

Autophagy is a conserved cellular degradation process that delivers cytoplasmic components to lysosomes for breakdown and recycling. It supports cellular homeostasis, adapts to nutrient stress, and participates in development, immunity, and aging. The term autophagi is an infrequently used plural form found in some texts, but autophagy is the standard term for the process.

There are three main forms of autophagy. Macroautophagy, usually referred to simply as autophagy, involves the formation of a double-membrane autophagosome that sequesters cargo and fuses with lysosomes for degradation. Microautophagy entails direct engulfment of cytosolic material by the lysosome through membrane invagination. Chaperone-mediated autophagy uses unfolded substrate proteins that are recognized by chaperones and translocated across the lysosomal membrane via the LAMP-2A receptor. Autophagy can be non-selective, or selective for particular cargo such as damaged mitochondria (mitophagy), ribosomes (ribophagy), or invasive pathogens (xenophagy).

Regulation of autophagy is driven by nutrient and stress signals. The process is controlled by autophagy-related (ATG) genes and a signaling network centered on mTOR, which inhibits initiation in nutrient-rich conditions. Under starvation or stress, AMPK activation and ULK1 complex induction promote autophagosome formation via class III PI3K (Beclin-1–VPS34) signaling, with LC3 becoming conjugated to the growing membrane. Cargo selection often involves adaptor proteins like p62/SQSTM1.

Biological roles of autophagy include cellular quality control, energy balance during starvation, and defense against infections. It is implicated in development, aging, neurodegenerative diseases, cancer, and immune responses. While generally cytoprotective, excessive or dysregulated autophagy can contribute to pathology or cell death in certain contexts.