Endophagy

Endophagy is a cellular process in which a cell internalizes material from its own interior, typically by invaginating a portion of the plasma membrane to form a vesicle that encloses cytoplasmic constituents. The term derives from the Greek words “endo‑” meaning “within” and “phagein” meaning “to eat,” and it is sometimes used interchangeably with intracellular autophagy, although the latter more commonly refers to the degradation of organelles and protein aggregates via lysosomal pathways.

The core mechanism of endophagy involves the coordinated action of membrane‑remodeling proteins, such as dynamin‑related GTPases, and cytoskeletal elements that drive membrane curvature and vesicle scission. In many eukaryotic cells, endophagic vesicles fuse with endosomes or lysosomes where their contents are broken down and recycled, contributing to cellular homeostasis, nutrient recycling, and response to stress. Variations of the process have been observed in specialized cell types, including certain immune cells that employ endophagy to capture and present intracellular antigens.

Research on endophagy has expanded since the early 2000s, revealing its role in disease contexts. Dysregulation of endophagic pathways is implicated in neurodegenerative disorders, where impaired clearance of misfolded proteins may exacerbate pathology, and in cancer, where altered vesicle trafficking can affect tumor metabolism and drug resistance. Pharmacological agents that modulate endophagic activity are under investigation as potential therapeutics, particularly compounds that enhance lysosomal function.

Endophagy is related to, but distinct from, processes such as phagocytosis (engulfment of extracellular particles) and macropinocytosis (nonspecific bulk uptake). Ongoing studies aim to delineate the molecular signatures that differentiate these pathways and to clarify how endophagy integrates with broader cellular quality‑control networks.