A5044229298- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- Metabolism and Genetic Disorders
- RNA Research and Splicing
- ATP Synthase and ATPases Research
- RNA modifications and cancer
- Italian Literature and Culture
- Diverse academic and cultural studies
- Linguistic Studies and Language Acquisition
- Educational and Social Studies
- Historical and Literary Analyses
- DNA Repair Mechanisms
- Medieval European Literature and History
- Psychoanalysis and Psychopathology Research
- French Urban and Social Studies
- Italian Social Issues and Migration
- Renaissance Literature and Culture
- Biochemical and Molecular Research
- Ubiquitin and proteasome pathways
- Redox biology and oxidative stress
- Genetic Neurodegenerative Diseases
- Infectious Encephalopathies and Encephalitis
- Nanopore and Nanochannel Transport Studies
- Social Representations and Identity
- Cardiac Arrest and Resuscitation
University of Bari Aldo Moro
2010-2025
Institut de Biosciences et Biotechnologies
2025
University of Siena
2024
Wellcome Centre for Mitochondrial Research
2012-2020
Newcastle University
2011-2020
Radboud University Medical Center
2018
Radboud University Nijmegen
2018
University of Sussex
2018
Ochsner Health System
2018
Center for Children
2018
Identifying the genetic basis for mitochondrial diseases is technically challenging given size of proteome and heterogeneity disease presentations. Using next-generation exome sequencing, we identified in a patient with severe combined respiratory chain defects corresponding perturbation protein synthesis, homozygous p.Arg323Gln mutation TRIT1. This gene encodes human tRNA isopentenyltransferase, which responsible i6A37 modification anticodon loops small subset cytosolic tRNAs. Deficiency...
The p.N478D missense mutation in human mitochondrial poly(A) polymerase (mtPAP) has previously been implicated a form of spastic ataxia with optic atrophy. In this study, we have investigated fibroblast cell lines established from family members. homozygous resulted the loss polyadenylation all transcripts assessed; however, oligoadenylation was retained. Interestingly, had differential effects on transcript stability that were dependent particular species transcript. These changes...
In mammals, NRF-2 (nuclear respiratory factor 2), also named GA-binding protein, is an Ets family transcription that controls many genes involved in cell cycle progression and protein synthesis as well mitochondrial biogenesis. this paper, we analyzed the role of regulation human DNA replication. By a combination bioinformatic biochemical approaches, found binds vitro vivo to proximal promoter region coding for termination mTERF, RNA polymerase POLRMT, B subunit polymerase-gamma, helicase...
The Escherichia coli oligoribonuclease, ORN, has a 3' to 5' exonuclease activity specific for small oligomers that is essential cell viability. human homologue, REXO2, hitherto been incompletely characterized, with only its in vitro ability degrade single-stranded RNA and DNA fragments documented. Here we show the enzyme clear dual cellular localization being present both cytosolic mitochondrial fractions. Interestingly, form localizes intermembrane space matrix. Depletion of REXO2 by...
Pediatric diffuse intrinsic pontine glioma (DIPG), classified under midline glioma, is a deadly tumor, with no effective treatments. The human mitochondrial protease hClpP potential DIPG therapeutic target, and this study describes the synthesis of two new series tetrahydropyridopyrimidindiones (THPPDs) as activators. Among tested compounds, we have identified 36 (THX6) that shows strong activation (EC50 = 1.18 μM) good cytotoxicity in ONC201-resistant cells (IC50 0.13 μM). Studying...
<h3>Objective</h3> To address the relationship between mutations in DNA strand break repair protein tyrosyl phosphodiesterase 2 (TDP2) and spinocerebellar ataxia autosomal recessive 23 (SCAR23) to characterize cellular phenotype of primary fibroblasts from this disease. <h3>Methods</h3> We have used exome sequencing, Sanger gene editing cell biology, biochemistry, subcellular mitochondrial analyses for study. <h3>Results</h3> identified a patient United States with SCAR23 harboring same...
The nuclear-encoded glycyl-tRNA synthetase gene (GARS) is essential for protein translation in both cytoplasm and mitochondria. In contrast, different genes encode the mitochondrial cytosolic forms of most other tRNA synthetases. Dominant GARS mutations were described inherited neuropathies, while recessive cause severe childhood-onset disorders affecting skeletal muscle heart. downstream events explaining tissue-specific phenotype–genotype relations remained unclear. We investigated...
In recent years, an increasing number of mitochondrial disorders have been associated with mutations in aminoacyl-tRNA synthetases (mt-aaRSs), which are key enzymes protein synthesis. Bi-allelic functional variants VARS2, encoding the valyl tRNA-synthetase, were first reported a patient psychomotor delay and epilepsia partialis continua oxidative phosphorylation (OXPHOS) Complex I defect, before being described neonatal form encephalocardiomyopathy. Here we provide detailed genetic,...
In mammalian mitochondria, the processing of primary RNA transcripts involves a coordinated series cleavage and modification events, leading to formation intermediates mature mt-RNAs. RNA19 is an unusually stable unprocessed precursor, physiologically polyadenylated, which includes 16S mt-rRNA, mt-tRNALeuUUR mt-ND1 mRNA. These peculiarities, together with alteration its steady-state levels in cellular models defects mitochondrial function, make potentially important molecule for...
In mammalian mitochondria, messenger RNA is processed and matured from large primary transcripts in structures known as granules. The identity of the factors process transferring mRNA to mitoribosome for translation unclear. Nascent mature are believed associate initially with small mitoribosomal subunit prior recruitment form translationally active monosome. When fails assemble, however, stability mt‐mRNA only marginally affected, under these conditions, LRPPRC/SLIRP RNA‐binding complex has...
The MTERF family is a large protein family, identified in metazoans and plants, which consists of four subfamilies, MTERF1, 2, 3 4. Mitochondrial localisation was predicted for the vast majority members demonstrated characterised proteins. main structural feature proteins presence modular architecture, based on repetitions 30-residue module, mTERF motif, containing leucine zipper-like heptads. includes transcription termination factors: human mTERF, sea urchin mtDBP Drosophila DmTTF. In...
Autosomal dominant progressive external ophthalmoplegia (adPEO) is a late-onset, Mendelian mitochondrial disorder characterised by paresis of the extraocular muscles, ptosis, and skeletal-muscle restricted multiple DNA (mtDNA) deletions. Although dominantly inherited, pathogenic variants in POLG, TWNK RRM2B are among most common genetic defects adPEO, identification novel candidate genes underlying pathomechanisms remains challenging. We report clinical, molecular investigations patient who...
The m.3243A>G mutation within the mitochondrial mt-tRNALeu(UUR) gene is most prevalent variant linked to encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome. This pathogenic causes severe impairment of protein synthesis due alterations mutated tRNA, such as reduced aminoacylation a lack post-transcriptional modification. In transmitochondrial cybrids, overexpression human leucyl-tRNA synthetase (LARS2) has proven effective in rescuing phenotype associated...
The DREF [DRE (DNA replication-related element)-binding factor], which regulates the transcription of a group cell proliferation-related genes in Drosophila, also controls expression three involved mtDNA (mitochondrial DNA) replication and maintenance. In present study, by silico analysis, we have identified DREs promoter region gene participating transcription, DmTTF (Drosophila mitochondrial termination factor). Transient transfection assays Drosophila S2 cells, with mutated versions...