UNIVERSITÄT ZU KÖLN

Elena Rugarli
CECAD Research Center/Institute for Genetics
University of Cologne

E-mail: elena.rugarliuni-koeln.de
Phone: +49 - 221 / 478 84244
For more information and contact please visit the RUGARLI LAB.

Running time within the CRC 1218: 07/2016 - 06/2028.
 

Abstract

Regulation of mitochondrial biogenesis and function is essential during development and adult life. Post-transcriptional mechanisms enable fast and adaptive responses to tailor mitochondrial gene expression to changing cellular needs. We showed that the CLUH (clustered mitochondrial homolog) protein binds mRNAs encoding for a subset of mitochondrial proteins. Loss of CLUH leads to destabilization of its target mRNAs and to a depletion of the corresponding proteins from mitochondria. Previously, we have demonstrated the physiological requirement of CLUH in the mouse in several tissues. We now aim to elucidate the molecular basis of how CLUH binds and regulates its target mRNAs.

Project-related publications

Zaninello M, Schlegel T, Nolte H, Pirzada M, Savino E, Barth E, Klein I, Wüstenberg H, Uddin T, Wolff L, Wirth B, Lehmann HC, Cioni JM, Langer T, Rugarli EI (2024). CLUH maintains functional mitochondria and translation in motoneuronal axons and prevents peripheral neuropathy. Sci Adv. 10(22):eadn2050. DOI: 10.1126/sciadv.adn2050. 

Montoro-Gámez, C., Nolte, H., Molinié, T., Evangelista, G., Tröder, S., Barth, E., Popovic, M., Trifunovic, A., Zevnik, B., Langer, T., Rugarli E.I. SARM1 deletion delays cerebellar but not spinal cord degeneration in an enhanced mouse model of SPG7 deficiency. Brain. 2023 Apr 22:awad136. doi: 10.1093/brain/awad136. Online ahead of print. PMID: 37086482

Patron, M., Tarasenko, D., Nolte, H., Ghosh, M.,  Ohba, Y., Lasarzewski, Y., Ahmadi, Z.A., Cabrera-Orefice, A., Eyiama, A., Kellermann, T., Rugarli, E.I., Brandt, U., Meinecke, M., Langer, T. (2022). Regulation of mitochondrial proteostasis by the proton gradient. The EMBO Journal (2022)e110476. https://doi.org/10.15252/embj.2021110476

Schatton, D., Di Pietro, G., Szczepanowska, K., Veronese, M., Marx, M.-C., Braunöhler, K., Esther, B., Müller, S., Giavalisco, P., Langer, T., Trifunovic, A., Rugarli, I.E. (2022). CLUH controls astrin-1 expression to couple mitochondrial metabolism to cell cycle progression. Elife. 2022 May 13;11:e74552. DOI: 10.7554/eLife.74552

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

Aravamudhan, S., Türk, C., Bock, T., Keufgens, L., Nolte, H., Lang, F., Krishnan, R.K., König, T., Hammerschmidt, P., Schindler, N., Brodesser, S., Rozsivalova, D.H., Rugarli, E., Trifunovic, A., Brüning, J., Langer, T., Braun, T., Krüger, M. (2021). Phosphoproteomics of the developing heart identifies PERM1 - An outer mitochondrial membrane protein.  2021 Feb 5;154:41-59. doi.org/10.1016/j.yjmcc.2021.01.010

Pla-Martin, D.,  Schatton, D., Wiederstein, J.L., Marx, M.C.,  Khiati, S., Krüger, M., Rugarli, E.I. (2020). CLUH granules coordinate translation of mitochondrial proteins with mTORC1 signaling and mitophagy. EMBO J. e102731. doi.org/10.15252/embj.2019102731. [Epub ahead of print]

Murru, S., Hess, S., Barth, E., Almajan, E.R., Schatton, D., Hermans, S., Brodesser, S., Langer, T., Kloppenburg, P., Rugarli, E.I. (2019). Astrocyte-specific deletion of the mitochondrial m-AAA protease reveals glial contribution to neurodegeneration. GLIA 67, 1526-1541.

Sprenger, H.G., Wani, G., Hesseling, A., König, T., Patron, M., MacVicar, T., Ahola, S., Wai, T., Barth, E., Rugarli, E.I., Bergami, M., Langer, T. (2019). Loss of the mitochondrial i‐AAA protease YME1L leads to ocular dysfunction and spinal axonopathy. EMBO Mol Med. pii: e9288. doi: 10.15252/emmm.201809288. [Epub ahead of print]

Schatton, D. and Rugarli, E.I. (2018). A concert of RNA-binding proteins coordinates mitochondrial function. Crit. Rev. Biochem. Mol. Biol. 53, 652-666.

Schatton, D., and Rugarli, E.I. (2018). Post-transcriptional regulation of mitochondrial function. Curr. Opin. Physiol. 3, 6-15.

Schatton, D., Pla-Martin, D., Marx, M.C., Hansen, H., Mourier, A., Nemazanyy, I., Pessia, A., Zentis, P., Corona, T., Kondylis, V., Barth, E., Schauss, A.C., Velagapudi, V., and Rugarli, E.I. (2017). CLUH regulates mitochondrial metabolism by controlling translation and decay of target mRNAs. J. Cell Biol. 216, 675-693. doi: 10.1083/jcb.201607019.

Wang, S., Jacquemyn, J., Murru, S., Martinelli, P., Barth, E., Langer, T., Niessen, C.M., and Rugarli, E.I. (2016). The mitochondrial m-AAA protease prevents demyelination and hair greying. PLoS Genet 12, e1006463.

Gao, J., Schatton, D., Martinelli, P., Hansen, H., Pla-Martin, D., Barth, E., Becker, C., Altmueller, J., Frommolt, P., Sardiello, M., and Rugarli, E.I. (2014). CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins. J. Cell Biol. 207, 213-223.

Kondadi, A.K., Wang, S., Montagner, S., Kladt, N., Korwitz, A., Martinelli, P., Herholz, D., Baker, M.J., Schauss, A.C., Langer, T., and Rugarli, E.I. (2014). Loss of the m-AAA protease subunit AFG3L2 causes mitochondrial transport defects and tau hyperphosphorylation. EMBO J. 33, 1011-1026.