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ATG2A-mediated DAG transfer recruits DGAT2 for lipid droplet growth

ABSTRACT:

Lipid droplet (LD) growth mechanisms and the roles of LD-associated lipid transfer proteins remain poorly understood. Here, we show that the autophagy lipid transfer protein ATG2A has an anabolic role and promotes LD expansion by transferring diacylglycerol (DAG), and potentially triacylglycerol (TAG) and phosphatidic acid (PA), from the endoplasmic reticulum (ER) to LDs. In ATG2A deficiency, synthesized lipids are incorporated inefficiently into LDs and assemble new LDs. Additionally, diacylglycerol acyltransferase 2 (DGAT2), which synthesizes TAG and expands LD, fails to relocate to LDs. In vitro, DAG recruits DGAT2 to LDs. These findings support the idea that ATG2A-mediated DAG transfer recruits DGAT2 to LDs, promoting LD expansion. ATG2A alone promotes LD growth by transferring TAG and DAG, but its effectiveness in LD expansion is reduced when DGAT2 is inhibited. This synergistic action with DGAT2 prevents the buildup of non-membrane lipids within the ER and favors TAG synthesis on the LD surface.

INSTRUMENT(S): Liquid Chromatography MS -

PROVIDER: MTBLS12951 | MetaboLights | 2025-09-07

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS12951_LC-MS___metabolite_profiling-1.txt	Txt
	a_MTBLS12951_LC-MS___metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS12951_LC-MS___metabolite_profiling-1_v2_maf.tsv	Tabular
	m_MTBLS12951_LC-MS___metabolite_profiling_v2_maf.tsv	Tabular

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