title: Cell Type-Specific Modulation of Respiratory Chain Supercomplex Organization.
abstract: Respiratory chain complexes are organized into large supercomplexes among which supercomplex In + IIIn + IVn is the only one that can directly transfer electrons from NADH to oxygen. Recently, it was reported that the formation of supercomplex In + IIIn + IVn in mice largely depends on their genetic background. However, in this study, we showed that the composition of supercomplex In + IIIn + IVn is well conserved in various mouse and human cell lines. Strikingly, we found that a minimal supercomplex In + IIIn, termed "lowest supercomplex" (LSC) in this study because of its migration at the lowest position close to complex V dimers in blue native polyacrylamide gel electrophoresis, was associated with complex IV to form a supercomplex In + IIIn + IVn in some, but not all of the human and mouse cells. In addition, we observed that the 3697G>A mutation in mitochondrial-encoded NADH dehydrogenase 1 (ND1) in one patient with Leigh's disease specifically affected the assembly of supercomplex In + IIIn + IVn containing LSC, leading to decreased cellular respiration and ATP generation. In conclusion, we showed the existence of LSC In + IIIn + IVn and impairment of this supercomplex causes disease.
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China. dayansun0128@163.com.
authors.forename: Dayan
authors.initials: D
authors.lastname: Sun
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China. zblibin123@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China. 15167797018@163.com.
authors.forename: Ruyi
authors.initials: R
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China. FangH@WMU.edu.cn.
authors.forename: Hezhi
authors.initials: H
authors.lastname: Fang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China. ljx@wmu.edu.cn.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lyu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D042963:Electron Transport Complex II / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000378:metabolism*; D005260:Female; D006801:Humans; D007888:Leigh Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008930:Mitochondria, Liver / Q000378:metabolism; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D055503:Protein Multimerization
chemical_list: C478189:respiratory complex II; D000255:Adenosine Triphosphate; D042963:Electron Transport Complex II; D009245:NADH Dehydrogenase; D014450:Electron Transport Complex III
keywords: Leigh’s disease; mitochondrial dysfunction; mitochondrial supercomplex; nuclear genetic background; respiratory chain