Evidence mapPaperPMID 42498720Full record

ArticleCell death and differentiation2026

PLIN2-PGAM5-regulated lipid droplet-mitochondria contacts drive microglial neuroinflammation after spinal cord injury via fatty acid metabolic reprogramming.

Daoqiang Huang, Hong Li, Yiqian Luo, Pan Jiang, Haojie Zhang, Dingzhong Cheng, Longyou Xiao, Kuileung Tong, Jiale He, Zengbo Lu and 5 more

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Article in Cell death and differentiation, 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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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

15 authors.

Daoqiang Huang *Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.ORCID http://orcid.org/0000-0001-6407-3813
Hong Li *Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Yiqian Luo *Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.ORCID http://orcid.org/0000-0001-5442-4413
Pan Jiang *Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Haojie ZhangDepartment of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Dingzhong ChengDepartment of Orthopaedics, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Longyou XiaoDepartment of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Kuileung TongDepartment of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Jiale HeDepartment of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Zengbo LuDepartment of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Xuantao HuDepartment of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Mao PangDepartment of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. pangmao6@mail.sysu.edu.cn.
Senyu YaoDepartment of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. yaosy27@mail.sysu.edu.cn.ORCID http://orcid.org/0009-0001-7263-6281
Limin RongDepartment of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. ronglm@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0003-0373-7393
Bin LiuDepartment of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. liubin6@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0001-9295-8176

Funding

China Postdoctoral Science Foundation 2024M763769, 2025T180653China Postdoctoral Science Foundation 2024M763788National Natural Science Foundation of China (National Science Foundation of China) 82372400,82072455National Natural Science Foundation of China (National Science Foundation of China) U22A20297, 82572748, 82172433
6 · The paper itself

Abstract

Persistent neuroinflammation is a hallmark of central nervous system (CNS) injury, driving neuronal loss and functional deficits. While microglial lipid metabolic reprogramming, particularly lipid droplet accumulation, has been implicated in chronic inflammation, the underlying mechanisms remain poorly understood. Using single-cell transcriptomics, we identified a previously defined lipid droplet-accumulating microglia (LDAM) subpopulation in spinal cord injury (SCI), characterized by elevated PLIN2 expression. Genetic deletion of Plin2 markedly reduced lipid droplet burden, attenuated neuroinflammation, and promoted neuronal survival and functional recovery in vivo. Mechanistically, PLIN2 interacts with the mitochondrial outer membrane protein PGAM5 to regulate lipid droplet-mitochondria contacts. This interaction inverts canonical metabolic flux by redirecting fatty acids from mitochondria back to lipid droplets, thereby suppressing β-oxidation and inducing mitochondrial dysfunction, which subsequently triggers STING-dependent inflammation. Notably, the PLIN2 220-392 domain is essential for PGAM5 binding and contact formation; disrupting this interaction attenuates STING signaling and enhances neuroprotection and functional recovery in vivo. Our findings identify the PLIN2-PGAM5 as a critical metabolic-immune pathway and suggest that targeting organelle-contact-mediated metabolic reprogramming represents a potential therapeutic strategy for CNS injury.

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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 Socratic graph.