Cholesterol transfer proteins promote Atg-independent ER clearance by lysosomes.

Ruoxi Wang, Tina M Fortier, Xiaofeng Sun, Fei Chai, Panagiotis D Velentzas, Eric H Baehrecke

Abstract read

In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed

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1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Ruoxi WangDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Department of Neuroscience, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.

Tina M FortierDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.

Xiaofeng SunDepartment of Neuroscience, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.

Fei ChaiDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.

Panagiotis D VelentzasDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.

Eric H BaehreckeDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA. Electronic address: eric.baehrecke@umassmed.edu.

Funding

Regulation of autophagy during animal developmentR35GM131689 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Eric H Baehrecke · 2019 to 2026

$4.9M

NIGMS NIH HHS R35 GM131689

6 · The paper itself

Abstract

Selective removal of endoplasmic reticulum (ER) is important for cell health. Macroautophagy is the primary mechanism for the removal of the ER, but the ER can be cleared in a macroautophagy-independent manner. However, the physiological relevance and mechanisms underlying macroautophagy-independent ER clearance remain largely unknown. Here we show that ER is cleared by lysosomes in a macroautophagy Atg gene-independent manner during development. This developmentally programmed Atg-independent ER clearance by lysosomes requires the ER protein Vap33 that promotes ER and lysosome contact. Oxysterol-binding protein (Osbp) is known to associate with Vap33, and Osbp lysosomal localization is required for ER clearance in cells lacking macroautophagy. Significantly, the cholesterol transport-associated protein Start1 regulates ER and lysosome contact, macroautophagy-independent ER clearance, and cholesterol transport from ER to the lysosome. These studies reveal that Vap33, Osbp, and Start1 promote ER clearance by lysosomes that is associated with cholesterol trafficking.

Indexed as

Carrier ProteinsCholesterolDrosophila ProteinsEndoplasmic ReticulumLysosomesAnimalsDrosophila melanogasterHumansMacroautophagyOxysterol Binding ProteinsReceptors, SteroidVesicular Transport ProteinsCarrier ProteinsCholesterolDrosophila ProteinsOxysterol Binding ProteinsReceptors, SteroidVesicular Transport ProteinsCP: cell biologyDrosophilaERESCRTlysosomeOsbpStart1Vap33

Identifiers

PMID42258351

DOI10.1016/j.celrep.2026.117537

PMCPMC13358760

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.