APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size.

Autor:	Windham IA; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Powers AE; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Ragusa JV; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Wallace ED; Mass Spectrometry Core Laboratory, Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Zanellati MC; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Williams VH; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Wagner CH; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., White KK; Microscopy Services Laboratory, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Cohen S; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2024 Apr 01; Vol. 223 (4). Date of Electronic Publication: 2024 Feb 09.
DOI:	10.1083/jcb.202305003
Abstrakt:	The E4 variant of APOE strongly predisposes individuals to late-onset Alzheimer's disease. We demonstrate that in response to lipogenesis, apolipoprotein E (APOE) in astrocytes can avoid translocation into the endoplasmic reticulum (ER) lumen and traffic to lipid droplets (LDs) via membrane bridges at ER-LD contacts. APOE knockdown promotes fewer, larger LDs after a fatty acid pulse, which contain more unsaturated triglyceride after fatty acid pulse-chase. This LD size phenotype was rescued by chimeric APOE that targets only LDs. Like APOE depletion, APOE4-expressing astrocytes form a small number of large LDs enriched in unsaturated triglyceride. Additionally, the LDs in APOE4 cells exhibit impaired turnover and increased sensitivity to lipid peroxidation. Our data indicate that APOE plays a previously unrecognized role as an LD surface protein that regulates LD size and composition. APOE4 causes aberrant LD composition and morphology. Our study contributes to accumulating evidence that APOE4 astrocytes with large, unsaturated LDs are sensitized to lipid peroxidation, which could contribute to Alzheimer's disease risk. (© 2024 Windham et al.)
Databáze:	MEDLINE
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