title: Suppression of Mic60 compromises mitochondrial transcription and oxidative phosphorylation.
abstract: Precise regulation of mtDNA transcription and oxidative phosphorylation (OXPHOS) is crucial for human health. As a component of mitochondrial contact site and cristae organizing system (MICOS), Mic60 plays a central role in mitochondrial morphology. However, it remains unclear whether Mic60 affects mitochondrial transcription. Here, we report that Mic60 interacts with mitochondrial transcription factors TFAM and TFB2M. Furthermore, we found that Mic60 knockdown compromises mitochondrial transcription and OXPHOS activities. Importantly, Mic60 deficiency decreased TFAM binding and mitochondrial RNA polymerase (POLRMT) recruitment to the mtDNA promoters. In addition, through mtDNA immunoprecipitation (mIP)-chromatin conformation capture (3C) assays, we found that Mic60 interacted with mtDNA and was involved in the architecture of mtDNA D-loop region. Taken together, our findings reveal a previously unrecognized important role of Mic60 in mtDNA transcription.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100005, P.R. China.
authors.forename: Rui-Feng
authors.initials: RF
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100005, P.R. China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100005, P.R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100005, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100005, P.R. China.
authors.forename: Yu-Xuan
authors.initials: YX
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100005, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100005, P.R. China.
authors.forename: Zhu-Qin
authors.initials: ZQ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100005, P.R. China.
authors.forename: Hou-Zao
authors.initials: HZ
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100005, P.R. China.
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Liu
mesh_terms: D002460:Cell Line; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008780:Methyltransferases / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; C088548:IMMT protein, human; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; C499631:TFAM protein, human; D014157:Transcription Factors; D008780:Methyltransferases; C462443:TFB2M protein, human