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Series GSE74009 Query DataSets for GSE74009
Status Public on Jun 07, 2023
Title Mitochondrial transfer disrupts mTORC1/Akt signaling modulating biogenesis and respiration
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Mitochondrial DNA (mtDNA) mutations are a major cause of maternally-inherited disease and have no treatment. Prevention strategies are critically important, but current clinical approaches are far from satisfactory. Legislation has changed in the UK to permit the development of mitochondrial transfer in human embryos, but major concerns have been raised about the mis-match of nuclear and mtDNA from ‘three parents’, with late sequelae being passed through the germ-line to subsequent generations. Matching donor and recipient mtDNA haplogroups is the proposed solution, but the effects of ‘haplogroup matching’ have not been tested experimentally. Here we show major changes in the cellular transcriptome both between and within the major mtDNA haplogroups when mitochondria are transferred between cells on a fixed nuclear genetic background. Larger differences were seen between phylogenetically related sub-haplogroups J1 and J2 which differ by only six nucleotides, than between the major haplogroups and known pathogenic mtDNA mutations. mtDNA transfer altered key cell signaling pathways, most notably the mTOR/Akt and the inflammatory cascade. This affected mitochondrial biogenesis, oxygen consumption, and ATP synthesis, and was blocked by rapamycin. These findings identify a key mediator in retrograde nuclear-mitochondrial signaling which is sensitive to subtle changes in mtDNA sequence. Given the established role of mTOR in cancer, neurodegeneration, and metabolic disease, this provides a mechanism for the association between inherited mtDNA variants and common late onset diseases, and demonstrates unexpected and dramatic effects of mitochondrial transfer not corrected by close haplogroup matching.
Overall design 2 cell lines per haplogroup were included plus the recipient cell (Rho0, 143B, osteosarcoma)
Contributor(s) Gomez-Duran A, Hudson G, Xu Y, Santibanez-Koref M, Ruiz-Pesini E, Chinnery PF
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Submission date Oct 14, 2015
Last update date Jun 07, 2023
Contact name Aurora Gomez Duran
Phone 696876193
Organization name Centro de Investigaciones Biologicas
Department Molecular Biomedicine
Lab MitoPhenomics
Street address Maria maeztu
City Madrid
State/province Madrid
ZIP/Postal code 28040
Country Spain
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (9)
GSM1908039 Rho0_143B
GSM1908040 Cybrid1_J2
GSM1908041 Cybrid2_J2
BioProject PRJNA298735
SRA SRP064803

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Supplementary file Size Download File type/resource
GSE74009_gencodeV19_gene_count_Rho0_and_haplo.txt.gz 2.7 Mb (ftp)(http) TXT
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