Publications by authors named "J P Di Rago"
Pentatricopeptide repeat (PPR) proteins bind RNA and are present in mitochondria and chloroplasts of Eukaryota. In fungi, they are responsible for controlling mitochondrial genome expression, mainly on the posttranscriptional level. Candida albicans is a human opportunistic pathogen with a facultative anaerobic metabolism which, unlike the model yeast Saccharomyces cerevisiae, possesses mitochondrially encoded respiratory Complex I (CI) subunits and does not tolerate loss of mtDNA.
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- 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.
Proving with certainty that a GFP-tagged protein is imported inside mitochondria by visualizing its fluorescence emission with an epifluorescence microscope is currently impossible using regular GFP-tagging. This is particularly true for proteins dual localized in the cytosol and mitochondria, which have been estimated to represent up to one third of the established mitoproteomes. These proteins are usually composed of a surpassingly abundant pool of the cytosolic isoform compared to the mitochondrial isoform.
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- 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.