Journal of lipid researchApr 30, 2014

Atg2A and Atg14L proteins attach to fat storage droplets and early recycling membranes in human cancer cells

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Updated Mar 30, 2026

Abstract

Human Atg2A and Atg14L colocalize at lipid droplets and influence their size and number in human tumor cell lines.

Atg2A is specifically localized to lipid droplets that are positive for ADRP and can move along microtubules.
The localization of Atg2A to lipid droplets occurs independently of whether autophagy is active.
Under nutrient-rich conditions, Atg2A and Atg14L are found together, suggesting a functional relationship.
Upon nutrient starvation, both proteins are recruited to early autophagosomal membranes, which is linked to the generation of a specific lipid, phosphatidylinositol 3-phosphate.
Atg2A and Atg14L may have roles beyond autophagy, including involvement in lipid metabolism.

Simplified

Autophagy is a lysosomal bulk degradation pathway for cytoplasmic cargo, such as long-lived proteins, lipids, and organelles. Induced upon nutrient starvation, autophagic degradation is accomplished by the concerted actions of autophagy-related (ATG) proteins. Here we demonstrate that two ATGs, human Atg2A and Atg14L, colocalize at cytoplasmic lipid droplets (LDs) and are functionally involved in controlling the number and size of LDs in human tumor cell lines. We show that Atg2A is targeted to cytoplasmic ADRP-positive LDs that migrate bidirectionally along microtubules. The LD localization of Atg2A was found to be independent of the autophagic status. Further, Atg2A colocalized with Atg14L under nutrient-rich conditions when autophagy was not induced. Upon nutrient starvation and dependent on phosphatidylinositol 3-phosphate [PtdIns(3)P] generation, both Atg2A and Atg14L were also specifically targeted to endoplasmic reticulum-associated early autophagosomal membranes, marked by the PtdIns(3)P effectors double-FYVE containing protein 1 (DFCP1) and WD-repeat protein interacting with phosphoinositides 1 (WIPI-1), both of which function at the onset of autophagy. These data provide evidence for additional roles of Atg2A and Atg14L in the formation of early autophagosomal membranes and also in lipid metabolism.

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Atg2A and Atg14L proteins attach to fat storage droplets and early recycling membranes in human cancer cells

Abstract

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