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Coronaviral ORF6 protein mediates inter-organelle contacts and modulates host cell lipid flux for virus production

ABSTRACT: Lipid droplets (LDs) form inter-organelle contacts with the endoplasmic reticulum (ER) that promote their biogenesis, while lipid droplet contacts with mitochondria enhance β-oxidation of contained fatty acids. Viruses have been shown to take advantage of lipid droplets to promote viral production, but it remains unclear whether they also modulate the interactions between LDs and other organelles. Here, we showed that coronavirus ORF6 protein targets lipid droplets and is localized to the mitochondria-LD and ER-LD contact sites, where it regulates LD biogenesis and lipolysis. At the molecular level, we find that that ORF6 inserts into the LD lipid monolayer via its two amphipathic helices. ORF6 further interacts with ER membrane proteins BAP31 and USE1 to mediate ER-LDs contact formation. Additionally, ORF6 interacts with the SAM complex in the mitochondrial outer membrane to link mitochondria to LDs. In dong so, ORF6 promotes cellular lipolysis and lipid droplet biogenesis to reprogram host cell lipid flux and facilitate viral production

SUBMITTER: Mengzhen Yue

PROVIDER: S-SCDT-10_15252-EMBJ_2022112542 | biostudies-other |

REPOSITORIES: biostudies-other

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