Publications by authors named "D Tribouillard-Tanvier"
The identification of a point mutation (p.Ser59Leu) in the CHCHD10 gene was the first genetic evidence that mitochondrial dysfunction can trigger motor neuron disease. Since then, we have shown that this mutation leads to the disorganization of the MItochondrial contact site and Cristae Organizing System (MICOS) complex that maintains the mitochondrial cristae structure.
View Article and Find Full Text PDFN-terminal ends of polypeptides are critical for the selective co-translational recruitment of N-terminal modification enzymes. However, it is unknown whether specific N-terminal signatures differentially regulate protein fate according to their cellular functions. In this work, we developed an in-silico approach to detect functional preferences in cellular N-terminomes, and identified in S.
View Article and Find Full Text PDFArticle 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.