{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["27(2)"],"submitter":["Shan Z"],"funding":["Fundamental Research Funds for the Central Universities","National Natural Science Foundation of China"],"pubmed_abstract":["A high ratio of severe mitochondrial defects causes multiple human mitochondrial diseases. However, until now, the <i>in vivo</i> rescue signal of such mitochondrial defect effects has not been clear. Here, we built fly mitochondrial defect models by knocking down the essential mitochondrial genes <i>dMterf4</i> and <i>dMrps23</i>. Following genome-wide RNAi screens, we found that knockdown of <i>Med8/Tfb4/mtSSB/PolG2/mtDNA-helicase</i> rescued <i>dMterf4/dMrps23</i> RNAi-mediated mitochondrial defect effects. Extremely surprisingly, they drove mtDNA replication outside mitochondria through the Med8/Tfb4-mtSSB/PolG2/mtDNA-helicase axis to amplify cytosolic mtDNA, leading to activation of the cGAS-Sting-like IMD pathway to partially mediate <i>dMterf4</i>/<i>dMrps23</i> RNAi-triggered effec"],"journal":["iScience"],"pagination":["108970"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10844862"],"repository":["biostudies-literature"],"pubmed_title":["mtDNA extramitochondrial replication mediates mitochondrial defect effects."],"pmcid":["PMC10844862"],"pubmed_authors":["Li S","Jian C","Shan Z","Zuo H","Gao Y","Zhao G","Ti X","Wang Y","Zhang Q"],"additional_accession":[]},"is_claimable":false,"name":"mtDNA extramitochondrial replication mediates mitochondrial defect effects.","description":"A high ratio of severe mitochondrial defects causes multiple human mitochondrial diseases. However, until now, the <i>in vivo</i> rescue signal of such mitochondrial defect effects has not been clear. Here, we built fly mitochondrial defect models by knocking down the essential mitochondrial genes <i>dMterf4</i> and <i>dMrps23</i>. Following genome-wide RNAi screens, we found that knockdown of <i>Med8/Tfb4/mtSSB/PolG2/mtDNA-helicase</i> rescued <i>dMterf4/dMrps23</i> RNAi-mediated mitochondrial defect effects. Extremely surprisingly, they drove mtDNA replication outside mitochondria through the Med8/Tfb4-mtSSB/PolG2/mtDNA-helicase axis to amplify cytosolic mtDNA, leading to activation of the cGAS-Sting-like IMD pathway to partially mediate <i>dMterf4</i>/<i>dMrps23</i> RNAi-triggered effec","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2025-04-22T03:17:42.227Z","creation":"2025-04-05T20:40:36.212Z"},"accession":"S-EPMC10844862","cross_references":{"pubmed":["38322987"],"doi":["10.1016/j.isci.2024.108970"]}}