A5060124837- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- Epigenetics and DNA Methylation
- ATP Synthase and ATPases Research
- RNA modifications and cancer
- Cell death mechanisms and regulation
- Renal and related cancers
- Pancreatic function and diabetes
- Cancer Research and Treatments
- Signaling Pathways in Disease
- Heat shock proteins research
- Cancer, Lipids, and Metabolism
- Amino Acid Enzymes and Metabolism
- Trace Elements in Health
- Renal cell carcinoma treatment
- Bioinformatics and Genomic Networks
- FOXO transcription factor regulation
- Microbial Metabolic Engineering and Bioproduction
- Chemotherapy-induced organ toxicity mitigation
- Cancer Cells and Metastasis
- Optimism, Hope, and Well-being
- PI3K/AKT/mTOR signaling in cancer
- Histone Deacetylase Inhibitors Research
- Cancer-related Molecular Pathways
- Garlic and Onion Studies
Medical Research Council
2013-2024
University of Cambridge
2014-2024
MRC Cancer Unit
2014-2024
University of Liverpool
2024
Hutchison/MRC Research Centre
2013-2023
University of Padua
2008-2021
Veneto Institute of Molecular Medicine
2009-2013
Sapporo Kosei General Hospital
2013
Instytut Biologii Doświadczalnej im. Marcelego Nenckiego
2012
Hospital Clínic de Barcelona
2011
Abstract Mutations in the tricarboxylic acid (TCA) cycle enzyme fumarate hydratase (FH) are associated with a highly malignant form of renal cancer. We combined analytical chemistry and metabolic computational modelling to investigate implications FH loss immortalized primary mouse kidney cells. Here, we show that accumulation caused by inactivation leads oxidative stress is mediated formation succinicGSH, covalent adduct between glutathione. Chronic succination GSH, FH, or exogenous...
We studied human cancer cell models in which we detected constitutive activation of ERK. A fraction active ERK was found to be located mitochondria RWPE-2 cells, obtained by v-Ki-Ras transformation the epithelial prostate RWPE-1 line; metastatic DU145 cells; and osteosarcoma SAOS-2 cells. All these tumor cells displayed marked resistance death caused apoptotic stimuli like arachidonic acid BH3 mimetic EM20-25, cause through mitochondrial permeability transition pore (PTP). PTP...
At least a third of the patients with pheochromocytoma (PCC) or paraganglioma (PGL) harbor an underlying germline mutation in known PCC/PGL gene. Mutations genes (SDHB, SDHD, SDHC, and SDHA) encoding component tricarboxylic acid cycle, succinate dehydrogenase (SDH), are major cause inherited PCC PGL. SDHB mutations also, albeit less frequently, associated renal cell carcinoma. Inactivation SDH another cycle component, fumarate hydratase (FH), have both been abnormalities cellular metabolism,...
// Giulia Guzzo 1 , Marco Sciacovelli 1, 2 Paolo Bernardi Andrea Rasola CNR Neuroscience Institute and Department of Biomedical Sciences, University Padova, 35121 Italy Medical Research Council Cancer Unit, Cambridge, Hutchison/MRC Centre, United Kingdom Correspondence to: Rasola, e-mail: rasola@bio.unipd.it Keywords: TRAP1, mitochondria, chaperones, cancer metabolism, ROS, succinate dehydrogenase Received: August 11, 2014 Accepted: September 13, Published: November 15, ABSTRACT TRAP1 is a...
Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid (TCA) cycle mutated in hereditary and sporadic cancers. Despite recent advances understanding its role tumorigenesis, effects FH loss on mitochondrial metabolism are still unclear. Here, we used mouse human cell lines to assess function FH-deficient cells. We found that cells exhibit decreased respiration, accompanied by a varying degree dysfunction respiratory chain (RC) complex I II. Moreover, show fumarate induces succination...
Abstract Glutamoptosis is the induction of apoptotic cell death as a consequence aberrant activation glutaminolysis and mTORC1 signaling during nutritional imbalance in proliferating cells. The role bioenergetic sensor AMPK glutamoptosis not defined yet. Here, we show that reactivation blocks both glutamine-dependent vitro vivo. We also glutamine used for asparagine synthesis GABA shunt to produce ATP inhibit AMPK, independently glutaminolysis. Overall, our results indicate metabolism...
Survival of tumor cells is favored by mitochondrial changes that make death induction more difficult in a variety stress conditions, such as exposure to chemotherapeutics. These are not fully characterized mitochondria, and include unbalance the redox equilibrium, inhibition permeability transition pore (PTP) opening through kinase signaling pathways modulation members Bcl-2 protein family. Here we show novel chemotherapeutic, Gold(III)-dithiocarbamato complex AUL12, induces oxidative cell...
// Francesco Ciscato 1,2 Marco Sciacovelli 1,3 , Gianmarco Villano 2 Cristian Turato Paolo Bernardi 1 Andrea Rasola Patrizia Pontisso CNR Institute of Neuroscience and Department Biomedical Sciences, University Padova, Italy; Medicine, Italy 3 present address: Medical Research Council Cancer Unit, Hutchison/MRC Centre, Hills Road, Cambridge, United Kingdom Correspondence: Rasola, email: Keywords : SERPINB3; chemotherapeutics; mitochondria; respiratory complexes; reactive oxygen species; cell...
Tubulointerstitial kidney disease is an important cause of progressive renal failure whose aetiology incompletely understood. We analysed a large pedigree with maternally inherited tubulointerstitial and identified homoplasmic substitution in the control region mitochondrial genome (m.547A>T). While mutations mtDNA coding sequence are well recognised affecting multiple organs, have never been shown to disease. Strikingly, our patients did not classical features Patient fibroblasts showed...
Metabolic reprogramming is critical for tumor initiation and progression. However, the exact impact of specific metabolic changes on cancer progression poorly understood. Here, we integrate multimodal analyses primary metastatic clonally-related clear cell renal cells (ccRCC) grown in physiological media to identify key stage-specific vulnerabilities. We show that a VHL loss-dependent branched-chain amino acid catabolism sustains de novo biosynthesis aspartate arginine enabling with...
Antamanide is a cyclic decapeptide derived from the fungus Amanita phalloides. Here we show that antamanide inhibits mitochondrial permeability transition pore, central effector of cell death induction, by targeting pore regulator cyclophilin D. Indeed, (i) inhibition not additive with D-binding drug cyclosporin A, (ii) inhibitory action on requires phosphate, as previously shown for A; (iii) ineffective in mitochondria or cells D null animals, and (iv) abolishes CyP-D peptidyl-prolyl...
Cancer is a multifaceted disease in which inherited genetic variants can be important drivers of tumorigenesis. The discovery that germline mutations metabolic genes predispose to familial forms cancer caused shift our understanding how metabolism contributes tumorigenesis, providing evidence alterations oncogenic. In this review, we focus on mitochondrial enzymes whose cancer, and fully appraise their involvement formation progression. Elucidating the molecular mechanisms orchestrate...
Tumor cells display metabolic alterations when compared to non-transformed cells. These characteristics are crucial for tumor development, maintenance and survival providing energy supplies molecular precursors. Anaplerosis is the property of replenishing TCA cycle, hub carbon metabolism, participating in biosynthesis precursors building blocks or signaling molecules. In advanced prostate cancer, an upshift succinate-driven oxidative phosphorylation via mitochondrial Complex II was reported....
Deregulated signal transduction and energy metabolism are hallmarks of cancer both play a fundamental role in tumorigenesis. While it is increasingly recognised that signalling highly interconnected, the underpinning mechanisms their co-regulation still largely unknown. Here we designed acquired proteomics, phosphoproteomics, metabolomics experiments fumarate hydratase (FH) deficient cells developed computational modelling approach to identify putative regulatory phosphorylation-sites...
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a syndrome caused by inactivating germline mutations in fumarate hydratase (FH) subsequent accumulation of fumarate. Fumarate leads to profound epigenetic changes the activation an anti-oxidant response via nuclear translocation transcription factor NRF2. The extent which chromatin remodeling shapes this currently unknown. Here, we explored effects FH loss on landscape identify networks involved remodeled FH-deficient cells. We FOXA2...