脂滴线粒体束缚释放MAVS抑制，增强抗病毒免疫
Lipid droplet-mitochondria tethering releases MAVS inhibition to potentiate antiviral immunity.
摘要(中文译文)
线粒体抗病毒信号蛋白（MAVS）形成朊病毒样聚集体以激活针对RNA病毒的天然免疫，但MAVS的代谢调控机制仍知之甚少。本研究表明，病毒感染诱导脂滴（LDs）形成，脂滴与线粒体发生物理相互作用，从而促进MAVS朊病毒样聚集体的组装。机制上，脂滴驻留蛋白PLIN3与线粒体融合蛋白MFN2结合，从而解除MFN2对MAVS的抑制作用并使其能够寡聚化。此外，脂滴-线粒体接触位点促进脂肪酸转移，维持MAVS信号传导所需的线粒体膜电位。富含油酸（OA）的饮食增强脂滴形成并在体内增强抗病毒免疫，而髓系特异性Seipin（脂滴生物发生调节因子）缺陷则减弱MAVS激活并加剧病毒易感性。这些发现确立了脂滴作为代谢平台，通过细胞器间交互作用将细胞脂质代谢与天然抗病毒防御相连接，提示诱导脂滴形成可作为一种新型抗病毒治疗策略。
Abstract
Mitochondrial antiviral signaling protein (MAVS) forms prion-like aggregates to activate innate immunity against RNA viruses, but the metabolic regulation of MAVS remains poorly understood. Here, we show that viral infection induces the formation of lipid droplets (LDs), which physically interact with mitochondria to promote the assembly of MAVS prion-like aggregates. Mechanistically, the LD-resident protein PLIN3 binds to the mitochondrial fusion protein MFN2, thereby relieving MFN2-mediated inhibition of MAVS and enabling its oligomerization. Furthermore, LD-mitochondria contact sites facilitate fatty acid transfer, sustaining mitochondrial membrane potential required for MAVS signaling. Oleic acid (OA)-enriched diets enhance LD formation and boost antiviral immunity in vivo, while myeloid-specific Seipin (an LD biogenesis regulator) deficiency attenuates MAVS activation and exacerbates viral susceptibility. These findings establish LDs as metabolic platforms that bridge cellular lipid metabolism with innate antiviral defense through organelle crosstalk, suggesting LD induction as a novel therapeutic strategy against viruses.
如何引用
AMA
Qianwen Peng, Wenbo Liang, Wei Wang, Jie Wang, Qi Wang, Chunyuan Zhao, et al. Lipid droplet-mitochondria tethering releases MAVS inhibition to potentiate antiviral immunity.. Cell reports. 2026; doi:10.1016/j.celrep.2026.117601.
APA
Qianwen Peng, Wenbo Liang, Wei Wang, Jie Wang, Qi Wang, Chunyuan Zhao, et al (2026). Lipid droplet-mitochondria tethering releases MAVS inhibition to potentiate antiviral immunity.. Cell reports. https://doi.org/10.1016/j.celrep.2026.117601
GB/T 7714
Qianwen Peng, Wenbo Liang, Wei Wang, Jie Wang, Qi Wang, Chunyuan Zhao, et al. Lipid droplet-mitochondria tethering releases MAVS inhibition to potentiate antiviral immunity.[J]. Cell reports, 2026 doi:10.1016/j.celrep.2026.117601.
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