A5036507823- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- ATP Synthase and ATPases Research
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Metabolomics and Mass Spectrometry Studies
- DNA Repair Mechanisms
- Coenzyme Q10 studies and effects
- Photosynthetic Processes and Mechanisms
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Genetics and Neurodevelopmental Disorders
- Biochemical and Molecular Research
- Ubiquitin and proteasome pathways
- Neurogenesis and neuroplasticity mechanisms
- Lysosomal Storage Disorders Research
- Soft tissue tumor case studies
- Genomics and Phylogenetic Studies
- interferon and immune responses
- Viral Infections and Immunology Research
- Botanical Research and Chemistry
- Rheology and Fluid Dynamics Studies
- Angiogenesis and VEGF in Cancer
- Vitamin C and Antioxidants Research
- Body Contouring and Surgery
Universidad de Zaragoza
2015-2024
Instituto de Investigación Sanitaria Aragón
2017-2024
Centre for Biomedical Network Research on Rare Diseases
2018-2024
Instituto de Investigación de Enfermedades Raras
2024
Instituto de Salud Carlos III
2024
Centro de Investigación Biomédica en Red
2018-2022
University of Miami
2003-2005
Montreal Neurological Institute and Hospital
2005
McGill University
2005
Frequently, mtDNA with pathogenic mutations coexist wild-type genomes (mtDNA heteroplasmy). Mitochondrial dysfunction and disease ensue only when the proportion of mutated mtDNAs is high, thus a reduction in this should provide an effective therapy for these disorders. We developed system to decrease specific haplotypes by expressing mitochondrially targeted restriction endonuclease, ApaLI, cells heteroplasmic mice. These mice have two haplotypes, which one contains ApaLI site. After...
The existence of reliable mtDNA reference sequences for each species is great relevance in a variety fields, from phylogenetic and population genetics studies to pathogenetic determination variants humans or animal models mtDNA-linked diseases. We present compelling evidence the sequencing errors on current mouse sequence. This includes deletion full codon two genes, substitution one amino acid five occasions also involvement tRNA rRNA genes. conclusions are supported by: (i) re-sequencing...
We have restored the CoQ oxidative capacity of mouse mtDNA-less cells (rho degrees cells) by transforming them with alternative oxidase Aox Emericella nidulans. Cotransforming rho NADH dehydrogenase Saccharomyces cerevisiae, Ndi1 and recovered DH/CoQ reductase activities. oxidation AOX reduces dependence on pyruvate uridine. Coexpression NDI1 further improves recycling NAD(+). Therefore, 2 single-protein enzymes restore electron transport in mammalian mitochondria substituting >80 nuclear...
Complex I (CI) is the largest enzyme of mammalian mitochondrial respiratory chain. The biogenesis complex a very process due to its large size and number subunits (45 subunits). situation further complicated fact that have double genomic origin, as seven them are encoded by DNA. Understanding assembly characterization involved factors has advanced much in last years. However, until now, key part process, is, how at which step mitochondrially CI (ND subunits) incorporated was not known....
In the present work, a large scale investigation was done regarding capacity of cultured human cell lines (carrying in homoplasmic form either mitochondrial tRNALysA8344G mutation associated with myoclonic epilepsy and ragged red fiber (MERRF) encephalomyopathy or frameshift mutation, isolatedin vitro, gene for ND4 subunit NADH dehydrogenase) to undergo transcomplementation their recessive DNA (mtDNA) mutations after fusion. The presence appropriate nuclear drug resistance markers two...
Abstract Background Most patients suffering from Leber hereditary optic neuropathy carry one of the three classic pathologic mutations, but not all individuals with these genetic alterations develop disease. There are different risk factors that modify penetrance mutations. The remaining a set very rare variants and, it appears that, some classical mutations may also affect phenotype other Results We describe large family including 95 maternally related individuals, showing 30 neuropathy....
Many patients suffering late-onset Alzheimer disease show a deficit in respiratory complex IV activity. The de novo pyrimidine biosynthesis pathway connects with the mitochondrial chain upstream from IV. We hypothesized that these would have decreased nucleotide levels. Then, different cell processes for which compounds are essential, such as neuronal membrane generation and maintenance synapses production, be compromised. Using model, we inhibiting oxidative phosphorylation function reduces...
Down syndrome is the most common genomic disorder of intellectual disability and caused by trisomy chromosome 21. Several genes in this repress mitochondrial biogenesis. The goal study was to evaluate whether early overexpression these may cause a prenatal impairment oxidative phosphorylation negatively affecting neurogenesis. Reduction energy production lower function have been reported diverse tissues or cell types, also at any age, including fetuses, suggesting that defect an general...
The study of pathogenic mitochondrial DNA mutations has, in most cases, relied on the production transmitochondrial cybrids. Although procedure to produce such cybrids is well established, it laborious and cumbersome. Moreover, mechanical enucleation inefficient different techniques have be used depending adherence properties cell. To circumvent these difficulties, we developed a chemical method that can wide applicability for based use actinomycin D render nuclear genome...
Nuclear and mitochondrial genomes have to work in concert generate a functional oxidative phosphorylation (OXPHOS) system. We previously shown that we could restore partial OXPHOS function when chimpanzee or gorilla DNA (mtDNA) were introduced into human cells lacking mtDNA. However, unable maintain orangutan cell. now produced chimpanzee, gorilla, orangutan, baboon mtDNA attempted introduce from different apes them. Surprisingly, able an nuclear background, even though these showed severe...
The vision loss in Leber hereditary optic neuropathy patients is due to mitochondrial DNA mutations. No treatment has shown a clear-cut benefit on clinically meaningful end-point. However, clinical evidences suggest two therapeutic approaches: the reduction of mutation load heteroplasmic or elevation amount homoplasmic patients.Here we show that ketogenic treatment, cybrid cell lines, reduces percentage m.13094 T > C and also increases levels m.11778G A genotype.These results diet could be...
The onset of Leber hereditary optic neuropathy is relatively rare in childhood and, interestingly, the rate spontaneous visual recovery very high this group patients. Here, we report a child harboring pathological mitochondrial DNA mutation, present heteroplasmy, associated with disease. A patient follow-up showed rapid vision accompanied by decrease percentage mutated mtDNA. retrospective study on age all childhood-onset patients reported literature suggested that process was probably...
We present a new hypothesis on the contribution of dysfunction oxidative phosphorylation system, through decrease in de novo synthesis pyrimidine nucleotides, to pathogenesis late onset Alzheimer's disease (AD). In light this proposition, different treatments for AD patients, such as enhancing electron flow downstream coenzyme Q10 mitochondrial respiratory chain or increasing biogenesis directly providing pyrimidines, would be possible. is multifactorial disorder and not all patients benefit...
Several homoplasmic pathologic mutations in mitochondrial DNA, such as those causing Leber hereditary optic neuropathy or non-syndromic hearing loss, show incomplete penetrance. Therefore, other elements must modify their pathogenicity. Discovery of these modifying factors is not an easy task because multifactorial diseases conventional genetic approaches may always be informative. Here, we have taken evolutionary approach to unmask putative for a particular mutation aminoglycoside-induced...
Encephalomyopathic mtDNA depletion syndrome 13 (MTDPS13) is a rare genetic disorder caused by defects in F-box leucine-rich repeat protein 4 (FBXL4). Although FBXL4 essential for the bioenergetic homeostasis of cell, precise role remains unknown. In this study, we report two cases unrelated patients presenting neonatal period with hyperlactacidemia and generalized hypotonia. Severe was detected muscle biopsy both patients. Genetic analysis showed one patient as having compound heterozygosis...