Gutierrez 2012 Hum Mutat
| Gutiérrez Cortés N, Pertuiset C, Dumon E, Börlin M, Hebert-Chatelain E, Pierron D, Feldmann D, Jonard L, Marlin S, Letellier T, Rocher C (2012) Novel mitochondrial DNA mutations responsible for maternally inherited non-syndromic hearing loss. Hum Mutat [Epub ahead of print]. |
Gutiérrez Cortés N, Pertuiset C, Dumon E, Börlin M, Hebert-Chatelain E, Pierron D, Feldmann D, Jonard L, Marlin S, Letellier T, Rocher C (2012) Hum Mutat
Abstract: Some cases of maternally inherited isolated deafness are caused by mtDNA mutations, frequently following an exposure to aminoglycosides. Two mitochondrial genes have been clearly described as being affected by mutations responsible for this pathology: the ribosomal RNA 12S gene and the transfer RNA Serine (UCN) gene. A previous study identified several candidate novel mtDNA mutations, localized in a variety of mitochondrial genes, found in patients with no previous treatment with aminoglycosides (Leveque, et al., 2007). Five of these candidate mutations are characterized in the present study. These mutations are localized in subunit ND1 of complex I of the respiratory chain (m.3388C>A (p.MT-ND1:Leu28Met)), the tRNA for Isoleucine (m.4295A>G), subunit COII of complex IV (m.8078G>A (p.MT-CO2:Val165Ile)), the tRNA of Serine 2 (AGU/C) (m.12236G>A) and Cytochrome B, subunit of complex III (m.15077G>A (p.MT-CYB:Glu111Lys)). Cybrid cell lines have been constructed for each of the studied mtDNA mutations and functional studies have been performed to assess the possible consequences of these mutations on mitochondrial bioenergetics. This study shows that a variety of mitochondrial genes, including protein coding genes, can be responsible for non-syndromic deafness, and that exposure to aminoglycosides is not required to develop the disease, giving new insights on the molecular bases of this pathology. • Keywords: Cybrid cell lines, ribosomal RNA 12S gene, transfer RNA Serine (UCN) gene, subunit ND1 of complex I, subunit COII of complex IV, Cytochrome B subunit of complex III
Labels:
Stress:Mitochondrial Disease; Degenerative Disease and Defect"Mitochondrial Disease; Degenerative Disease and Defect" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property., Genetic Defect; Knockdown; Overexpression"Genetic Defect; Knockdown; Overexpression" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: z in prep"z in prep" is not in the list (Human, Pig, Mouse, Rat, Guinea pig, Bovines, Horse, Dog, Rabbit, Cat, ...) of allowed values for the "Mammal and model" property., Human Tissue;cell: z in prep"z in prep" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property. Preparation: z in prep"z in prep" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property. Enzyme: Complex I, Complex III, Complex IV; Cytochrome c Oxidase"Complex IV; Cytochrome c Oxidase" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property. Regulation: z in prep"z in prep" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
HRR: Oxygraph-2k
