Supplementary data for: IRG1/itaconate inhibits microglial senescence-like transition by modulating mitochondrial dynamics through RhoA alkylation in subarachnoid hemorrhage

Aging is a potent risk factor for poor prognosis in subarachnoid hemorrhage (SAH), yet the molecular mechanisms underlying the age-related exacerbation of early brain injury remain incompletely understood. This study investigates the immunometabolic regulation of the microglial senescence-like transition following SAH, focusing on the immune-responsive gene 1 (IRG1)/itaconate axis. We observed that the endogenous upregulation of IRG1 and itaconate is a protective response to hemorrhagic stress that is significantly blunted in aged mice. Microglia-specific IRG1 deficiency exacerbated SAH-induced brain injury, characterized by an accelerated senescence-like transition and the secretion of senescence-associated secretory phenotype (SASP) factors. Mechanistically, we demonstrate that IRG1 deficiency leads to excessive mitochondrial fission and dysfunction via the hyperactivity of Dynamin-related protein 1 (Drp1). Using click chemistry-based proteomics and site-directed mutagenesis, we ident..., , # Supplementary data for: IRG1/itaconate inhibits microglial senescence-like transition by modulating mitochondrial dynamics through RhoA alkylation in subarachnoid hemorrhage Dataset DOI: [10.5061/dryad.9cnp5hr0x](https://doi.org/10.5061/dryad.9cnp5hr0x) ## Description of the data and file structure The data is in three files: Supplementary Table 3: Summary of statistical tests and exact p-values for all comparisons Supplementary Table 4: Drp1-related signaling molecules in PPI network Supplementary Table 5: Potential targets of cysteine alkylation modification by itaconate ### Files and variables #### File: Supplementary_Table_3.pdf **Description:**Â Summary of statistical tests and exact p-values for all comparisons #### File: Supplementary_Table_4.pdf **Description:**Â Drp1-related signaling molecules in PPI network #### File: Supplementary_Table_5.pdf **Description:**Â Potential targets of cysteine alkylation modification by itaconate ## Code/software Sumatra PDF Micro..., ,衰老是蛛网膜下腔出血（subarachnoid hemorrhage, SAH）患者预后不良的重要危险因素，但年龄相关的早期脑损伤加重的分子机制仍未完全阐明。本研究探讨了蛛网膜下腔出血后小胶质细胞样衰老转化的免疫代谢调控机制，聚焦于免疫应答基因1（immune-responsive gene 1, IRG1）/衣康酸轴。我们观察到，IRG1与衣康酸的内源性上调是对出血应激的保护性应答，而该应答在老年小鼠中显著减弱。小胶质细胞特异性IRG1缺陷会加重蛛网膜下腔出血诱导的脑损伤，表现为加速的小胶质细胞样衰老转化以及衰老相关分泌表型（senescence-associated secretory phenotype, SASP）因子的分泌。从机制层面而言，我们证实IRG1缺陷会通过动力相关蛋白1（Dynamin-related protein 1, Drp1）的过度活化引发线粒体过度裂变与功能障碍。本研究通过基于点击化学的蛋白质组学与定点诱变技术，鉴定出……，# 补充数据：蛛网膜下腔出血中IRG1/衣康酸通过RhoA烷基化调控线粒体动态以抑制小胶质细胞样衰老转化 数据集DOI：[10.5061/dryad.9cnp5hr0x](https://doi.org/10.5061/dryad.9cnp5hr0x) ## 数据与文件结构说明 本数据集包含3个文件： 补充表3：所有比较的统计学检验汇总及精确p值 补充表4：蛋白质相互作用（protein-protein interaction, PPI）网络中与Drp1相关的信号分子 补充表5：衣康酸介导的半胱氨酸烷基化修饰潜在靶点 ### 文件与变量 #### 文件：Supplementary_Table_3.pdf **说明：** 所有比较的统计学检验汇总及精确p值 #### 文件：Supplementary_Table_4.pdf **说明：** 蛋白质相互作用网络中与Drp1相关的信号分子 #### 文件：Supplementary_Table_5.pdf **说明：** 衣康酸介导的半胱氨酸烷基化修饰潜在靶点 ## 代码与软件 Sumatra PDF ……