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A05 | The role of CLUH in transport and translation of mRNAs for mitochondrial proteins

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

E-mail: elena.rugarliSpamProtectionuni-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 - 06/2024.


Regulation of mitochondrial biogenesis and function is essential during development and adult life. CLUH is an RNA-binding protein that binds a subset of transcripts encoding mitochondrial proteins, and plays a crucial role in allowing an efficient mitochondrial catabolic response at birth and during starvation. CLUH binds target mRNAs in specific granular compartments where it coordinates their stability and translational status in a spatio-temporal manner. We will investigate whether CLUH plays a role in transport and/or local translation of mRNAs encoding mitochondrial proteins. To this end, we will use as model system spinal motoneurons, which are characterised by long axons that depend on transport and local translation of mRNAs.

Project-related publications

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.