{"database":"iProX","file_versions":[],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["Lingling Zhou"],"species":["Mus Musculus"],"full_dataset_link":["http://www.iprox.org/page/project.html?id=IPX0014866000"],"submitter_email":["zhoulingling@njucm.edu.cn"],"submitter_affiliation":["Nanjing University of Chinese Medicine"],"sample_protocol":[""],"repository":["iProX"],"data_protocol":[""],"pubmed_abstract":["<h4>Background</h4>The mitochondrial unfolded protein response (UPR<sup>mt</sup>) maintains proteostasis, but its dysregulation dictates cell fate. This study aimed to elucidate the signaling mechanism by which triptolide (TP), a bioactive component of Tripterygium wilfordii Hook. f., triggers hepatocellular Lipoapoptosis, focusing on HSP60-mediated UPR<sup>mt</sup> overactivation.<h4>Methods</h4>A TP-induced mouse liver injury model was established. Serum biochemistry, histopathology, and liver proteomics were performed. Key proteins (HSP60, UPR<sup>mt</sup> components, SREBP-1c, FASN, cleaved caspase-3) were validated by Western blot and RT-qPCR both in vivo and in AML-12 hepatocytes, while co-immunoprecipitation (Co-IP) was conducted in AML-12 cells. Functional validation used siRNA knockdown.<h4>Results</h4>TP induced liver injury, lipid deposition, and apoptosis. Proteomic screening implicated UPR<sup>mt</sup> activation, with HSP60 subsequently validated as a central upregulated component. TP downregulated MFN2 and upregulated HSP60, ClpP, DRP1, SREBP-1c, FASN, and cleaved caspase-3. Co-IP confirmed a direct HSP60-SREBP-1c interaction. Moreover, HSP60 knockdown attenuated the entire TP-induced cascade, including UPR<sup>mt</sup> overactivation, mitochondrial dysfunction, lipid dysregulation, and apoptosis.<h4>Conclusion</h4>This study delineates a novel mitochondria-to-nucleus pathway wherein TP induces HSP60-mediated UPR<sup>mt</sup> overactivation, which promotes SREBP-1c/FASN-driven lipid accumulation, culminating in lipoapoptosis. The \"HSP60-UPR<sup>mt</sup>-SREBP-1c/FASN-lipoapoptosis\" axis links dysregulated organelle stress signaling to metabolic cell death. These findings establish HSP60 as a key signaling node and a potential therapeutic target for intercepting this pathological cascade."],"pubmed_title":["HSP60-mediated UPR&lt;sup&gt;mt&lt;/sup&gt; overactivation drives triptolide-induced hepatocellular lipoapoptosis."],"pubmed_authors":["Yu Zhichao Z, Hu Lan L, Ding Jing J, Li Xiang X, Zhang Qi Q, Zhang Qiaoyu Q, Chen Shuoyu S, Zhang Pei P, Zhang Jiaqi J, Jiang Baoping B, Zhou Xueping X, Zhou Lingling L"],"additional_accession":[]},"is_claimable":false,"name":"HSP60-mediated UPRmt overactivation drives  triptolide-induced  Hepatocellular lipoapoptosis","description":"This study aims to investigate the role of excessive activation of the mitochondrial unfolded protein response (UPRmt) in TP-induced liver injury and to elucidate the mechanism by which HSP60 mediates this process in regulating lipid metabolism disorders.","dates":{"publication":"Thu Jan 08 00:00:00 GMT 2026"},"accession":"PXD072797","cross_references":{"TAXONOMY":["10090"],"pubmed":["42119834"]}}