omegasomes

Omegasomes are transient, endoplasmic reticulum–derived membrane structures that are enriched in phosphatidylinositol 3-phosphate (PI3P) and serve as initiation sites for autophagosome formation during macroautophagy. They are most clearly observed in mammalian cells under autophagy-inducing conditions and are named for their omega-shaped appearance in fluorescence imaging.

Formation of omegasomes is driven by the class III phosphatidylinositol 3-kinase complex I (Vps34-Beclin1-ATG14L-VPS15), which generates PI3P at specific subdomains of the ER. PI3P then recruits effector proteins such as DFCP1 and the WIPI family that mark omegasomes and help organize downstream autophagy machinery. These events coordinate the recruitment of the Atg8/LC3 lipidation system, which is essential for expanding and closing the phagophore, the precursor to the autophagosome.

Functionally, an omegasome acts as a nucleation platform for the phagophore, guiding membrane elongation and shaping the developing autophagosome. The assembly process links membrane sources from the ER with autophagy-related proteins to ensure proper enclosure of cytoplasmic cargo.

Dynamics and significance vary with cellular context. Omegasomes are dynamic and usually transient, forming during conditions that trigger autophagy, such as nutrient deprivation or pharmacological induction, and dissipating as autophagosomes mature. Their proper formation is important for efficient autophagic flux, and disruptions can affect the efficiency of autophagy in cells.