Time: Tuesday, 13/June/2023: 9:00am - 10:45am Session Chair: Jose Antonio Enriquez Session Chair: Daria Diodato |
Location: Bologna Congress Center - Sala Europa Address: Piazza della Costituzione, 4/a, Bologna (BO), Italy |
ID: 162
Invited Speakers
Fuels and drivers of smouldering brain disease
University of Cambridge, United Kingdom
1. MA Leone, et al., S Pluchino, L Peruzzotti-Jametti, AL Vescovi. Foetal Allogeneic Intracerebroventricular Neural Stem Cell Transplantation in People with Secondary Progressive Multiple Sclerosis: A phase I dose-escalation clinical trial. medRxiv https://doi.org/10.1101/2022.11.14.22282124;
2. R Hamel, et al., and S Pluchino. Time-resolved single-cell RNAseq profiling identifies a novel Fabp5-expressing subpopulation of inflammatory myeloid cells in chronic spinal cord injury. bioRxiv, doi.org/10.1101/2020.10.21.346635;
3. A Mottahedin, et al., S Pluchino, L Peruzzotti-Jametti, R Goodwin, C Frezza, M Murphy and T Krieg. Targeting succinate metabolism to decrease brain injury upon mechanical thrombectomy treatment of ischemic stroke. Redox Biology 2023; 59: 102600;
4. Peruzzotti-Jametti, et al., and S Pluchino. Neural stem cells traffic functional mitochondria via extracellular vesicles. PLoS Biol 2021, https://doi.org/10.1371/journal.pbio.3001166;
5. G Krzak, CM Willis, JA Smith, S Pluchino and L Peruzzotti-Jametti. Succinate receptor SUCNR1 (GPR91) - an emerging regulator of myeloid cell function in neuroinflammation. Trends Immunol 2021; 42(1): 45-58;
6 Pluchino S, Smith JA, Peruzzotti-Jametti L. Promises and Limitations of Neural Stem Cell Therapies for Progressive Multiple Sclerosis. Trends Mol Med 2020 Oct;26(10):898-912;
7. S Pluchino and JA Smith. Explicating Exosomes: reclassifying the rising stars in intercellular communication. Cell 2019 Apr 4;177(2):225-227;
8. L Peruzzotti-Jametti and S Pluchino. Targeting mitochondrial metabolism in neuroinflammation: towards a therapy for progressive multiple sclerosis? Trends Mol Med. 2018 Oct;24(10):838-855;
9. L Peruzzotti-Jametti, et al., and S Pluchino. Macrophage-Derived Extracellular Succinate Licenses Neural Stem Cells to Suppress Chronic Neuroinflammation. Cell Stem Cell 2018 Mar 1; 22(3): 355-368;
10. N Iraci, et al., and S Pluchino. Extracellular vesicles are independent metabolic units delivering functional Asparaginase-like protein 1. Nat Chem Biol 2017 Sep;13(9):951-955.
ID: 673
Invited Speakers
Immunometabolisms at the crossroad between inflammation and aging
CSIC- Consejo Superior de Investigaciones Cientificas, Spain
Biology Center “Severo Ochoa” (Madrid, Spain) since 2017. Her research goal is to identify new strategies to target immune cells for boosting systemic resilience to inflammaging, cellular senescence and age-related multimorbidity. She has obtained funding from the major European and Spanish funding organizations, including an European Research Council Starting Grant in 2016, and Consolidator Grant in 2022.
Among the more important discoveries from her lab:
1.Demonstration that mimicking age-associated mitochondrial dysfunction in T cells does not only recapitulate immunosenescence, but causes a general, body-wide deterioration of health with multiple aging-related features. These results place the metabolism of T cells at the crossroad between inflammation, senescence and aging, highlighting that immunometabolism can be a therapeutic target to delay aging.
2.Decoding the molecular mechanisms by which aged T cells contribute to inflammaging and age-related diseases
3.The above studies in her laboratory have allowed them to propose new therapeutic targets to delay age-related multimorbidity and to reverse aortic aneurysms and prevent sudden death due to aortic dissections
Her international leadership in the field is endorsed by having been an "Invited Speaker" at more than 60 conferences and international congresses in the last 5 years, including Gordon Conferences, Cold Spring Harbor Conferences, EMBO workshops, Keystone Symposium, and participating as a keynote speaker on several occasions.
She has been awarded with ,L’Oréal UNESCO for Women in Science (2015), and BANCO SABADELL AWARD for Biomedical Research (2022), Royal Spanish Acadamy of Science for Female Scientist among others.
ID: 491
Inflammation and Immunity as mitochondrial contributor to pathology
Dissecting the role of type I interferon signaling in microglial response in a mouse model of mitochondrial disease
1Institute of Neurosciences, Autonomous University of Barcelona, Barcelona, Spain; 2Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona, Barcelona, Spain; 3Clinical Neuroproteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Pamplona, Spain; 4Centro de Análisis Genómico, CNAG-CRG, Barcelona, Spain
Gella, A., Prada, P., Carrascal, M., Urpí, A., González-Torres, M., Abian, J., Sanz, E., & Quintana, A. (2020). Mitochondrial Proteome of Affected Glutamatergic Neurons in a Mouse Model of Leigh Syndrome. Frontiers in Cell and Developmental Biology, 8, 660.
ID: 323
Inflammation and Immunity as mitochondrial contributor to pathology
The contribution of cell free-mitochondrial DNA in the pathogenesis of MELAS syndrome
1IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Italy; 2Department of Biomedical and NeuroMotor Sciences, University of Bologna, Italy
ID: 182
Inflammation and Immunity as mitochondrial contributor to pathology
A novel role for the mitochondrial topoisomerase TOP1MT in mediating mtDNA release and cGAS-STING activation
1University of Calgary, Canada; 2National Institutes of Health; 3Texas A&M University; 4University of British Columbia
Al Khatib I, Deng J, Symes SA, Zhang H, Huang S, Pommier Y, Khan A, Gibson W, Shutt TE. Activation of the cGAS-STING innate immune response in cells with deficient mitochondrial topoisomerase TOP1MT. https://www.biorxiv.org/content/10.1101/2022.03.08.483326v1
Al Khatib I, Kerr M, Zhang H, Huang S, Pommier Y, Khan A, Shutt TE. Functional characterization of two variants in the mitochondrial topoisomerase gene TOP1MT that impact regulation of the mitochondrial genome. Journal of Biological Chemistry. 2022 Oct; 298(10):102420.
ID: 209
Inflammation and Immunity as mitochondrial contributor to pathology
Impaired inflammatory response to lipopolysaccharide in fibroblasts from patients with long-chain fatty acid oxidation disorders
1Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; 2Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Aarhus, Denmark; 3Department of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Aarhus, Denmark; 4Department of Experimental Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; 5Core Facility Metabolomics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
Mosegaard S*, Dipace G*, Bross P, Carlsen J, Gregersen N, Olsen RKJ. 2020. ”Riboflavin Deficiency-Implications for General Human Health and Inborn Errors of Metabolism”. International Journal of Molecular Sciences;21(11):3847. doi: 10.3390/ijms21113847.
Mosegaard S*, Bruun GH*, Flyvbjerg KF, Bliksrud YT, Gregersen N, Dembic M, Annexstad E, Tangeraas T, Olsen RKJ, Andresen BS. 2017. “An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency”. Molecular Genetics and Metabolism;122(4):182-188. doi: 10.1016/j.ymgme.2017.10.014.
Olsen RKJ*, Koňaříková E*, Giancaspero TA*, Mosegaard S*, Boczonadi V*, Mataković L*, ….. Barile M, Prokisch H. 2016. ”Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency”. American Journal of Human Genetics;98(6):1130-1145. doi: 10.1016/j.ajhg.2016.04.006.
V.A. Yépez, M. Gusic, R. Kopajtich, C. Mertes, N.H. Smith, C.L. Alston, R. Ban, S. Beblo, R. Berutti, H. Blessing, E. Ciara, F. Distelmaier, P. Freisinger, J. Häberle, S.J. Hayflick, M. Hempel, Y.S. Itkis, Y. Kishita, T. Klopstock, T.D. Krylova, C. Lamperti, D. Lenz, C. Makowski, S. Mosegaard, M.F. Müller, G. Muñoz-Pujol, A. Nadel, A. Ohtake, Y. Okazaki, E. Procopio, T. Schwarzmayr, J. Smet, C. Staufner, S.L. Stenton, T.M. Strom, C. Terrile, F. Tort, R. Van Coster, A. Vanlander, M. Wagner, M. Xu, F. Fang, D. Ghezzi, J.A. Mayr, D. Piekutowska-Abramczuk, A. Ribes, A. Rötig, R.W. Taylor, S.B. Wortmann, K. Murayama, T. Meitinger, J. Gagneur, H. Prokisch, Clinical implementation of RNA sequencing for Mendelian disease diagnostics, Genome Med. 14 (2022) 38. https://doi.org/10.1186/s13073-022-01019-9.
Fogh S, Dipace G, Bie A, Veiga-da-Cunha M, Hansen J, Kjeldsen M, Mosegaard S, Ribes A, Gregersen N, Aagaard L, Van Schaftingen E, Olsen RKJ. “Variants in the ethylmalonyl-CoA decarboxylase (ECHDC1) gene: a novel player in ethylmalonic aciduria?” J Inherit Metab Dis. 2021 Sep;44(5):1215-1225. doi: 10.1002/jimd.12394.
Muru K., Reinson K., Künnapas K., Lilleväli H., Nochi Z., Mosegaard S., Pajusalu S., Olsen R. and Õunap K. “FLAD1 Asso-ciated Multiple Acyl-CoA Dehydrogenase Deficiency Identified by Newborn Screening.”. Molecular Genetics & Genomic Medicine;7(9). doi: 10.1002/mgg3.915.
García-Villoria J., de Azua B., Tort F., Mosegaard S., Matalonga L., Ugarteburu O., Teixidó L., Olsen R. and Ribes A. “FLAD1, a recently described gene associated to multiple acyl-CoA dehydrogenase deficiency (MADD) is mutated in a patient with myopathy, scoliosis and cataracts.”. Clinical Genetics;94(6):592-593. doi: 10.1111/cge.13452.
Auranen M., Paetau A., Piirilä P., Pohju A., Salmi T., Lamminen A., Thure H., Löfberg M., Mosegaard S., Olsen R., Tyni T. “FLAD1 gene mutation causes riboflavin responsive MADD disease”. Neuromuscular Disorders;27(6):581-584. doi: 10.1016/j.nmd.2017.03.003.
ID: 409
Inflammation and Immunity as mitochondrial contributor to pathology
Fumarate induces mtDNA release via mitochondrial-derived vesicles and drives innate immunity
1Medical Research Council, MBU,University of Cambridge, UK; 2Medical Research Council Cancer Unit,University of Cambridge, UK; 3CECAD Research Centre, University of Cologne, Cologne, Germany
AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology.
Tilokani L, Russell FM, Hamilton S, Virga DM, Segawa M, Paupe V, Gruszczyk AV, Protasoni M, Tabara LC, Johnson M, Anand H, Murphy MP, Hardie DG, Polleux F, Prudent J.
Sci Adv. 2022 Nov 11;8(45):eabo7956. doi: 10.1126/sciadv.abo7956. Epub 2022 Nov 11. PMID: 36367943
Mitochondrial translation is required for sustained killing by cytotoxic T cells.
Lisci M, Barton PR, Randzavola LO, Ma CY, Marchingo JM, Cantrell DA, Paupe V, Prudent J, Stinchcombe JC, Griffiths GM.
Science. 2021 Oct 15;374(6565):eabe9977. doi: 10.1126/science.abe9977. Epub 2021 Oct 15.
PMID: 34648346
Golgi-derived PI(4)P-containing vesicles drive late steps of mitochondrial division.
Nagashima S, Tábara LC, Tilokani L, Paupe V, Anand H, Pogson JH, Zunino R, McBride HM, Prudent J.
Science. 2020 Mar 20;367(6484):1366-1371. doi: 10.1126/science.aax6089.
PMID: 32193326
SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome.
Janer A, Prudent J, Paupe V, Fahiminiya S, Majewski J, Sgarioto N, Des Rosiers C, Forest A, Lin ZY, Gingras AC, Mitchell G, McBride HM, Shoubridge EA. EMBO Mol Med. 2016 Sep 1;8(9):1019-38. doi: 10.15252/emmm.201506159. Print 2016 Sep.
PMID: 27390132
CCDC90A (MCUR1) is a cytochrome c oxidase assembly factor and not a regulator of the mitochondrial calcium uniporter.
Paupe V, Prudent J, Dassa EP, Rendon OZ, Shoubridge EA.
Cell Metab. 2015 Jan 6;21(1):109-16. doi: 10.1016/j.cmet.2014.12.004.
PMID: 25565209
ID: 430
Inflammation and Immunity as mitochondrial contributor to pathology
Free cytosolic-mitochondrial DNA triggers a potent type-I Interferon response in Kearns–Sayre patients counteracted by mofetil mycophenolate
1Unit of Cellular Biology and Diagnosis of Mitochondrial Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; 2Division of Rheumatology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 3Division of Metabolism, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 4Research Unit of Muscular and Neurodegenerative Disorders, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy