A11 - Critical periods of mitochondrial structural and metabolic plasticity in Purkinje neurons
Elisa Motori
Institute for Biochemistry | University of Cologne
E-mail: elisa.motori@uni-koeln.de
Phone: +49 (0) 221 470 76 056
Running time within the CRC 1218: 10/2022 - 06/2028.
Abstract
Mitochondria are key regulators of cellular metabolism vital for the functioning and survival of neurons. To which extent mitochondrial segregation within specialized neuronal compartments (i.e., dendrites and axons) may reflect metabolically distinct functions is poorly understood. To address this question, we will examine by proteomics and metabolomics sorted mitochondrial fractions from dendritic and axonal terminals of mouse Purkinje neurons. We will then explore if functionally distinct mitochondrial pools underlie compartmentalized stress responses during disease, revealing novel aspects of metabolic vulnerability to neurodegeneration.
Project-related publications
Filograna R, Gerlach J, Choi HN, Rigoni G, Barbaro M, Oscarson M, Lee S, Tiklova K, Ringnér M, Koolmeister C, Wibom R, Riggare S, Nennesmo I, Perlmann T, Wredenberg A, Wedell A, Motori E, Svenningsson P, Larsson NG (2024). PARKIN is not required to sustain OXPHOS function in adult mammalian tissues. NPJ Parkinsons Dis. 10(1):93. DOI: 10.1038/s41531-024-00707-0.
Wani, G.A., Sprenger, H.-G., Ndoci, K., Chandragiri, S., Acton, R.J., Schatton, D., Kochan, S.M.V., Sakthivelu, V., Jevtic, M., Seeger, J.M., Müller, S., Giavalisco, P., Rugarli, E.I., Motori, E., Langer, T., Bergami, M. (2022). Metabolic control of adult neural stem cell self-renewal by the mitochondrial protease YME1L. Cell Reports • DOI:https://doi.org/10.1016/j.celrep.2022.110370
Motori E, Atanassov I, Kochan SMV, Folz-Donahue K, Sakthivelu V, Giavalisco P, Toni N, Puyal J, Larsson NG (2020). Neuronal metabolic rewiring promotes resilience to neurodegeneration caused by mitochondrial dysfunction. Sci Adv 6:eaba8271. DOI: 10.1126/sciadv.aba8271.
Gӧbel J, Engelhardt E, Pelzer P, Sakthivelu V, Jahn HM, Jevtic M, Folz-Donahue K, Kukat C, Schauss A, Frese CK, Giavalisco P, Ghanem A, Conzelmann KK, Motori E, Bergami M (2020). Mitochondria-Endoplasmic Reticulum Contacts in Reactive Astrocytes Promote Vascular Remodeling. Cell Metab 31:791-808 e798. DOI: 10.1016/j.cmet.2020.03.005.
Rumyantseva A, Motori E, Trifunovic A (2020). DARS2 is indispensable for Purkinje cell survival and protects against cerebellar ataxia. Hum Mol Genet 29:2845-2854. DOI: 10.1093/hmg/ddaa176.
Rangaraju V, Lewis TL, Jr., Hirabayashi Y, Bergami M, Motori E, Cartoni R, Kwon SK, Courchet J (2019). Pleiotropic Mitochondria: The Influence of Mitochondria on Neuronal Development and Disease. J Neurosci 39:8200-8208. DOI: 10.1523/JNEUROSCI.1157-19.2019.