Dataset Information

Proximity labeling on phosphatidic acid-enriched membranes generated via optogenetic membrane editing

ABSTRACT: Cellular lipid metabolism is subject to strong homeostatic regulation, but players involved in and mechanisms underlying these pathways remain mostly uncharacterized. Here, we develop and exploit a “Feeding-Fishing” approach coupling membrane editing using optogenetic lipid-modifying enzymes (feeding) with organelle membrane proteomics via proximity labeling (fishing) to elucidate molecular players and pathways involved in homeostasis of phosphatidic acid (PA), a multifunctional lipid central to glycerolipid metabolism. By performing proximity biotinylation using a membrane tethered TurboID alongside membrane editing to selectively deliver PA to the same membrane, we identified numerous PA-metabolizing enzymes and lipid transfer proteins enriched in and depleted from PA-fed membranes. Subsequent mechanistic analysis revealed that PA homeostasis in the cytosolic leaflets of the plasma membrane and lysosomes is mediated by both local PA metabolism and the action of members of the lipid transfer protein families that carry out interorganelle lipid transport prior to additional metabolic steps. More broadly, the interfacing of membrane editing with organelle membrane proteomics using proximity labeling represents a strategy for revealing mechanisms governing lipid homeostasis.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Qin Fu

LAB HEAD: Qin Fu

PROVIDER: PXD070378 | Pride | 2026-02-23

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	ReikaTei10445160_set3_12plex_Fr.mgf	Mgf
	ReikaTei10445160_set3_12plex_Fr.msf	Msf
	ReikaTei10445160_set3_12plex_Fr1.raw	Raw
	ReikaTei10445160_set3_12plex_Fr10.raw	Raw
	ReikaTei10445160_set3_12plex_Fr2.raw	Raw

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Publications

Membrane editing with proximity labeling reveals regulators of lipid homeostasis.

Tei Reika R Li Xiang-Ling XL Luan Lin L Baskin Jeremy M JM

Nature chemical biology 20260107

Cellular lipid metabolism is subject to strong homeostatic regulation, but the players involved in and mechanisms underlying these pathways remain largely uncharacterized. Here we develop a 'feeding-fishing' approach coupling membrane editing using optogenetic lipid-modifying enzymes (feeding) with organelle membrane proteomics through proximity labeling (fishing) to elucidate molecular players and pathways involved in the homeostasis of phosphatidic acid (PA), a multifunctional lipid central to ...[more]

PMID: 41501183

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