A5058903432- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- ATP Synthase and ATPases Research
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Glycogen Storage Diseases and Myoclonus
- RNA modifications and cancer
- HIV-related health complications and treatments
- Genomics and Rare Diseases
- Ubiquitin and proteasome pathways
- Coenzyme Q10 studies and effects
- Genetic Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Neurological diseases and metabolism
- RNA and protein synthesis mechanisms
- Hepatitis C virus research
- Liver Disease Diagnosis and Treatment
- Cardiomyopathy and Myosin Studies
- HIV Research and Treatment
- Alzheimer's disease research and treatments
- HIV/AIDS drug development and treatment
- Adrenal and Paraganglionic Tumors
- Peroxisome Proliferator-Activated Receptors
- Amino Acid Enzymes and Metabolism
Institut Cochin
2012-2022
Inserm
2012-2022
Centre National de la Recherche Scientifique
2012-2022
Université Paris Cité
2012-2022
Sorbonne Université
2009-2020
Assistance Publique – Hôpitaux de Paris
2008-2020
Hôpital Foch
2020
Lomonosov Moscow State University
2011-2020
Institut de Biologie Intégrative de la Cellule
2019
Hôpital Cochin
2010-2019
We investigated the correlations of deletions mitochondrial DNA in skeletal muscle with clinical manifestations myopathies, a group disorders defined either by biochemical abnormalities mitochondria or morphologic changes causing ragged red appearance fibers histochemically. performed genomic Southern blot analysis from 123 patients different myopathies encephalomyopathies. Deletions were found 32 patients, all whom had progressive external ophthalmoplegia. Some only ocular myopathy, whereas...
Mitochondrial fusion remains a largely unknown process despite its observation by live microscopy and the identification of few implicated proteins. Using green red fluorescent proteins targeted to mitochondrial matrix, we show that in human cells is efficient achieves complete mixing matrix contents within 12 h. This maintained absence functional respiratory chain, disruption microtubules or after significant reduction cellular ATP levels. In contrast, completely inhibited protonophores...
Two human Fzo-homologs, mitofusins Mfn1 and Mfn2, are shown by RT-PCR western blot to be ubiquitous mitochondrial proteins. Protease digestion experiments reveal that Mfn2 is an outer membrane protein with N-terminal C-terminal domains exposed towards the cytosol. The transmembrane of (Mfn2-TMCT) targeted mitochondria deletion these leads cytosolic localization truncated (Mfn2-NT). endoplasmic reticulum or when domain replaced short stretches neutral/hydrophobic (Mfn2-IYFFT) polar/basic...
Abstract Across a variety of Mendelian disorders, ∼50–75% patients do not receive genetic diagnosis by exome sequencing indicating disease-causing variants in non-coding regions. Although genome principle reveals all variants, their sizeable number and poorer annotation make prioritization challenging. Here, we demonstrate the power transcriptome to molecularly diagnose 10% (5 48) mitochondriopathy identify candidate genes for remainder. We find median one aberrantly expressed gene, five...
We studied the clinical, biochemical, and genetic features of eight patients with autosomal recessive mitochondrial syndrome neurogastrointestinal encephalomyopathy (MNGIE). MNGIE is clinically characterized by ophthalmoparesis, peripheral neuropathy, leukoencephalopathy, gastrointestinal symptoms (recurrent nausea, vomiting, or diarrhea) intestinal dysmotility, histologically abnormal mitochondria in muscle. Brain MRI scans were consistent leukodystrophy seven examined. Nerve conduction EMG...
Heteroplasmic mutations of mitochondrial DNA (mtDNA) are an important source human diseases. The mechanisms governing transmission, segregation and complementation heteroplasmic mtDNA-mutations unknown but depend on the nature dynamics compartment as well intramitochondrial organization mobility mtDNA. We show that mtDNA primary immortal cells is organized in several hundreds nucleoids contain a mean 2-8 mtDNA-molecules each. Nucleoids enriched transcription factor A distributed throughout...
Addition of hydrogen peroxide (H2O2) is a method commonly used to trigger cellular oxidative stress. However, the doses (often hundreds micromolar) are disproportionally high with regard physiological oxygen concentration (low micromolar). In this study using polarographic measurement in suspensions we show that H2O2 addition results O2 release as expected from catalase reaction. This reaction fast enough to, within seconds, decrease drastically and annihilate it few minutes. Firstly, likely...
Abstract Two biochemical deficits have been described in the substantia nigra Parkinson's disease, decreased activity of mitochondrial complex I and reduced proteasomal activity. We analysed interactions between these primary mesencephalic cultures. Proteasome inhibitors (epoxomicin, MG132) exacerbated toxicity [rotenone, 1‐methyl‐4‐phenylpyridinium (MPP + )] toxic dopamine analogue 6‐hydroxydopamine, but not II–V or excitotoxins [ N ‐methyl‐ d ‐aspartate (NMDA), kainate]. Rotenone MPP...
Abstract In Guadeloupe, epidemiological data have linked atypical parkinsonism with fruit and herbal teas from plants of the Annonaceae family, particularly Annona muricata . These contain a class powerful, lipophilic complex I inhibitors, annonaceous acetogenins. To determine neurotoxic potential these substances, we administered annonacin, major acetogenin A. , to rats intravenously Azlet osmotic minipumps (3.8 7.6 mg per kg day for 28 days). Annonacin inhibited in brain homogenates...
Abstract Reduced activity of the mitochondrial respiratory chain – particularly complex I may be implicated in etiology both Parkinson's disease and progressive supranuclear palsy, although these neurodegenerative diseases differ substantially as to their distinctive pattern neuronal cell loss predominance cerebral α‐synuclein or tau protein pathology. To determine experimentally whether chronic generalized inhibition has an effect on distribution tau, we infused rats systemically with...
Human OPA1 (optic atrophy type 1) is a dynamin-related protein of the mitochondrial IMS (intermembrane space) involved in membrane fusion and remodelling. Similarly to its yeast orthologue Mgm1p that exists two isoforms generated by serine protease Pcp1p/Rbd1p, various alternative splicing processing. In present paper, we focus on processing OPA1.We find mammalian cell types display similar pattern [two L-OPA1 (long OPA1) three S-OPA1 (short OPA1)] loss inner potential, but not inhibition...
Three patients born to the same set of consanguineous parents presented with antenatal skin oedema, hypotonia, cardiomyopathy and tubulopathy. The enzymatic activities multiple mitochondrial respiratory chain complexes were reduced in muscle. Marked reduction 12s rRNA, core small ribosomal subunit, was found fibroblasts. Homozygosity mapping led identification a mutation <i>MRPS22</i> gene, which encodes protein. Transfection patient cells wild-type cDNA increased rRNA content normalised...
Liver damage associated with chronic unexplained high serum transaminases in human immunodeficiency virus (HIV)-infected patients under combined antiretroviral therapy is unknown. histology was prospectively investigated presenting transaminase elevation for more than 6 months, after exclusion of alcohol abuse, hepatitis C (HCV) or B (HBV) infection, autoimmune, and genetic liver diseases. In a subgroup patients, mitochondrial activities were measured by spectrophotometry DNA (mtDNA)...
Loss-of-function mutations in PARK2/PARKIN and PINK1 cause early-onset autosomal recessive Parkinson disease (PD). The cytosolic E3 ubiquitin-protein ligase PARK2 cooperates with the mitochondrial kinase to maintain quality. A loss of transmembrane potential (ΔΨ) leads PINK1-dependent recruitment outer membrane (OMM), followed by ubiquitination proteasome-dependent degradation OMM proteins, autophagy-dependent clearance remnants. We showed here that blockade protein import triggers PARK2,...