A5035683701- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- ATP Synthase and ATPases Research
- interferon and immune responses
- Neuroscience and Neuropharmacology Research
- Genetics, Aging, and Longevity in Model Organisms
- Telomeres, Telomerase, and Senescence
- Protein Degradation and Inhibitors
- Circadian rhythm and melatonin
- Spaceflight effects on biology
- Endoplasmic Reticulum Stress and Disease
- Retinal Development and Disorders
- Protein Tyrosine Phosphatases
- Autophagy in Disease and Therapy
- Selenium in Biological Systems
- Sirtuins and Resveratrol in Medicine
- Coenzyme Q10 studies and effects
- MicroRNA in disease regulation
- Child Nutrition and Feeding Issues
- Memory and Neural Mechanisms
- Cancer-related Molecular Pathways
- Cancer, Hypoxia, and Metabolism
- Retinal Diseases and Treatments
- Electron Spin Resonance Studies
- Cellular transport and secretion
International Institute of Molecular and Cell Biology
2020-2024
Instytut Biologii Doświadczalnej im. Marcelego Nenckiego
2014-2019
Polish Academy of Sciences
2014-2018
Cardiff University
2007-2012
The University of Texas Medical Branch at Galveston
2008
OPA1 is a ubiquitously expressed, nuclear dynamin-related GTPase, targeted to the inner mitochondrial membrane, which plays role in fusion. Mutations gene on chromosome 3q28-qter are associated with autosomal dominant optic atrophy (ADOA), most common inherited neuropathy, retinal ganglion cells (RGCs) lost and visual acuity impaired from an early age. We have generated novel ENU-induced mutant mouse carrying protein-truncating nonsense mutation opa1 order explore pathophysiology of ADOA....
Cancer cells can undergo stress-induced premature senescence, which is considered to be a desirable outcome of anticancer treatment. However, the escape from senescence and cancer cell repopulation give rise some doubts concerning effectiveness senescence-induced therapy. Similarly, it postulated that polyploidization connected with disease relapse. We postulate associated culprit atypical divisions leading regrowth. Accordingly, we aimed dissociate between these two phenomena. induced in...
// Malgorzata Piechota 1, * , Piotr Sunderland Adrianna Wysocka 3 Maria Nalberczak 2 A. Sliwinska Kasia Radwanska Ewa Sikora 1 Laboratory of Molecular Bases Aging, Nencki Institute Experimental Biology, Polish Academy Sciences, Warsaw 02-093, Poland Basis Behavior, Preclinical Studies in Neurodegenerative Diseases, Warsaw, These authors have contributed equally to this study Correspondence to: Piechota, email: m.piechota@nencki.gov.pl Keywords: aging, DNA damage response, neurons,...
Abstract E3 ubiquitin ligases recognize substrates through their short linear motifs termed degrons. While degron-signaling has been a subject of extensive study, resources for its systematic screening are limited. To bridge this gap, we developed DEGRONOPEDIA, web server that searches degrons and maps them to nearby residues can undergo ubiquitination disordered regions, which may act as protein unfolding seeds. Along with an evolutionary assessment degron conservation, the also reports on...
purpose. To examine retinal ganglion cell (RGC) and axonal abnormalities in an ENU-induced mutant mouse carrying a protein-truncating nonsense mutation OPA1. Mutations the OPA1 gene cause autosomal dominant optic atrophy (ADOA) which loss of RGCs followed by myelin degeneration nerve leads to progressive decrease visual acuity. methods. Ultrastructure was examined heterozygous mutants wild-type littermate controls at 6, 9, 24 months using electron microscopy. The RGC layer 6 months. results....
Retinal ganglion cell dendritic pruning has been reported in association with a 50% reduction Opa1 transcript and protein retinal neural tissue, which manifests as visual dysfunction the heterozygous mutant mouse, B6;C3-Opa1Q285STOP. Here we report marked synaptic connectivity absence of soma loss explore mechanism relationship between mitochondrial integrity connectivity. We observed decreased levels postsynaptic density 95 Opa1+/− mice consistent inner plexiform layer. Glutamatergic but...
Organismal functionality and reproduction depend on metabolic rewiring balanced energy resources.However, the crosstalk between organismal homeostasis fecundity associated paracrine signaling mechanisms are still poorly understood.Using Caenorhabditis elegans, we discovered that large extracellular vesicles (known as exophers) previously found to remove damaged subcellular elements in neurons cardiomyocytes released by body wall muscles (BWM) support embryonic growth.Exopher formation...
The brain circuits and synaptic processes that underlie alcohol addiction are currently the subject of intensive research. Here we focus on hippocampal circuitry show chemogenetic inhibition dentate gyrus (DG) during presentation alcohol-associated cues has long-lasting effects mice behavior. DG enhances seeking drinking, suggesting regulates addiction-related behaviors. To test this hypothesis, perform whole-cell patch-clamp recordings from granule cells look for electrophysiological...
Opa3 mRNA is expressed in all tissues examined to date, but currently the function of OPA3 protein unknown. Intriguingly, various mutations gene lead two similar diseases humans: autosomal dominant inherited optic atrophy and cataract (ADOAC) a metabolic condition; type 3-methylglutaconic aciduria (MGA). Early onset bilateral common characteristic both disorders; retinal ganglion cells are lost visual acuity impaired from an early age. In order investigate protein, we have generated novel...
The majority of patients with autosomal dominant optic atrophy (DOA) harbor pathogenic OPA1 mutations and certain missense mutations, mostly within the GTPase domain, have recently been shown to cause multiple mitochondrial DNA (mtDNA) deletions in skeletal muscle. This raises possibility that neuropathy could be result secondary mtDNA defects accumulating retinal ganglion cells (RGCs). To explore this hypothesis, authors looked for evidence dysfunction a mouse model DOA documented visual...
There is agreement that the biological properties of additionally hydroxylated analogs resveratrol (RVT) may be stronger compared with their parent drug. Here we examined effect a novel RVT derivative, 3,3′,4,4′-tetrahydroxy- trans -stilbene (3,3′,4,4′-THS), on replicative senescence human peritoneal mesothelial cells. The study showed 3,3′,4,4′-THS improves cell proliferative capacity and delays entry into control RVT-treated latter coincided decreased activity senescence-associated...
ABSTRACT The ubiquitin-proteasome system is a proteolytic pathway that removes damaged and unwanted proteins. Their selective turnover initiated by ubiquitin (Ub) attachment, mainly Ub ligases recognize substrates through their short linear motifs termed degrons. A degradation-targeting degron comprises nearby Ub-modified residue an intrinsically disordered region (IDR) involved in interaction with the proteasome. Degron-signaling has been studied over last decades, yet there are no...
The ubiquitin-proteasome system (UPS) governs the degradation of proteins by ubiquitinating their lysine residues. Our study focuses on deserts - regions in conspicuously low residues averting ubiquitin-dependent proteolysis. We spotlight prevalence among bacteria leveraging pupylation-dependent proteasomal degradation, and UPS eukaryotes. To further scrutinize this phenomenon, we focused human receptors VHL SOCS1 to ascertain if could limit ubiquitination within cullin-RING ligase (CRL)...
The ubiquitin-proteasome system (UPS) is critical for maintaining proteostasis, influencing stress resilience, lifespan, and thermal adaptability in organisms. In Caenorhabditis elegans , specific proteasome subunits activators, such as RPN-6, PBS-6, PSME-3, are associated with heat resistance, survival at cold (4°C), enhanced longevity moderate temperatures (15°C). Previously linked to improving we investigated the impact of sterility-inducing floxuridine (FUdR) on UPS functionality under...
ABSTRACT The ubiquitin-proteasome system (UPS) functionality is vital for proteostasis, contributing to stress resilience, lifespan, and thermal adaptability. In Caenorhabditis elegans , proteasome constituents such as the RPN-6 PBS-6 subunits or PSME-3 activator are respectively linked heat resistance, survival at low temperatures (4°C), longevity moderate cold (15°C). Since inhibition of germline stem cells proliferation associated with robust proteostasis in worms, we utilized floxuridine...
Purpose Autosomal dominant optic atrophy (ADOA) due to mutations in OPA1 is a slowly progressive neuropathy. ubiquitously expressed and plays key role mitochondrial fusion. Heterozygous Opa1 mutant mice (B6;C3-Opa1Q285STOP), with previously reported visual defects nerve changes on EM, were assessed for evidence of cellular effects retinal sequelae. Methods The level processing studied by Western blot. Membrane potential was JC-1 isolated mitochondria. Mitochondrial morphology investigated...
Purpose Autosomal dominant optic atrophy (ADOA) due to mutations in OPA1 is a slowly progressive neuropathy. ubiquitously expressed and plays key role mitochondrial fusion. Heterozygous Opa1 mutant mice (B6;C3-Opa1Q285STOP), with previously reported visual defects nerve changes, were assessed for retinal sequelae. Methods ERGs VEPs recorded 12 month old B6;C3-Opa1Q285STOP (n=4) age/sex matched wildtype littermate controls. Full scotopic photopic intensity series response brief (4 ms) single...