Publications by authors named "A Dautant"
Article Synopsis
- The study highlights the increasing number of mitochondrial DNA (mtDNA) variants linked to neurodegenerative diseases and the challenges in assessing their impact, especially when present alongside normal mtDNA.
- Saccharomyces cerevisiae (yeast) is utilized as a model organism to analyze the effects of specific mtDNA variants on mitochondrial function due to its ability to support genetic transformations and similar mitochondrial protein function.
- Out of eight investigated MT-ATP6 gene variants in yeast, three variants (m.8950G>A, m.9025G>A, and m.9029A>G) showed significant defects in growth and ATP production, indicating potential pathogenicity, while the other five variants had little to no effect on mitochondrial function.
Article Synopsis
- The m.9032T>C mitochondrial DNA mutation has been linked to NARP, causing reduced ATP synthesis and increased oxidative stress in affected patients.
- This mutation results in a critical amino acid change (L169P) in ATP synthase, impairing its function in transporting protons for ATP production.
- Research using a yeast model with a similar mutation (L186P) showed that while the enzyme assembled properly, it was largely inactive, but intragenic suppressors were found that partially restored its function.
Article Synopsis
- Many diseases in humans are linked to mutations in the mitochondrial genome (mtDNA), which is crucial for producing energy through oxidative phosphorylation (OXPHOS).
- mtDNA mutations can have severe effects, particularly in energy-demanding tissues, and their pathogenicity is complicated by the phenomenon of heteroplasmy, where a cell contains a mix of mutant and normal mitochondrial DNA.
- The yeast Saccharomyces cerevisiae serves as an effective model to study these human mtDNA mutations since it allows for genome manipulation and offers insights into the consequences of specific mutations on energy production and potential therapeutic discoveries.
The yeast mitochondrial ATP synthase is an assembly of 28 subunits of 17 types of which 3 (subunits 6, 8, and 9) are encoded by mitochondrial genes, while the 14 others have a nuclear genetic origin. Within the membrane domain (FO) of this enzyme, the subunit 6 and a ring of 10 identical subunits 9 transport protons across the mitochondrial inner membrane coupled to ATP synthesis in the extra-membrane structure (F1) of ATP synthase. As a result of their dual genetic origin, the ATP synthase subunits are synthesized in the cytosol and inside the mitochondrion.
View Article and Find Full Text PDFThe human ATP synthase is an assembly of 29 subunits of 18 different types, of which only two (a and 8) are encoded in the mitochondrial genome. Subunit a, together with an oligomeric ring of c-subunit (c-ring), forms the proton pathway responsible for the transport of protons through the mitochondrial inner membrane, coupled to rotation of the c-ring and ATP synthesis. Neuromuscular diseases have been associated to a number of mutations in the gene encoding subunit a, ATP6.
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