Project 05:
Mechanisms of mitochondrial proximal translation and co-translational protein import
Yury Bykov
E-Mail: yury.bykov@rptu.de
Phone: +49 631-205-2885
Department of Biology
Rhineland-Palatinate Technical University of Kaiserslautern-Landau (RPTU)
Simone Mattei
E-Mail: simone.mattei@embl.de
Phone: +49 6221-387-8973
Imaging Centre
European Molecular Biology Laboratory
Abstract
Most of mitochondrial proteins are synthesized on the cytosolic ribosomes and then imported into the organelle. Some of them are made by the ribosomes that are located directly on the cytosolic surface of mitochondria. It is not known how the proteins are selected to be translated on the surface and if such translation leads to immediate import of the protein. The function of this process and its role in the mitochondrial biogenesis remains debated. In this project, we want to use a combination of in vivo assays and yeast genetics to find the mechanisms that sort proteins for local translation on the mitochondrial surface. We also will directly observe translating ribosomes by cryogenic in situ tomography.
Project-relevant publications
Bykov YS, Zuttion S, Senger B, Klein O, Asraf Y, Meyer H, Becker HD, Kucharczyk R, Schuldiner M (2024) A systematic bi-genomic split-GFP assay illuminates the mitochondrial matrix proteome and protein targeting routes. bioRxiv [Preprint] https://doi.org/10.1101/2024.04.17.589881.
Adamoski D, Dias MM, Quesñay JEN, Yang Z, Zagoriy I, Steyer AM, Rodrigues CT, da Silva Bastos AC, da Silva BN, Costa RKE, de Abreu FMO, Islam Z, Cassago A, van Heel MG, Consonni SR, Mattei S, Mahamid J, Portugal RV, Ambrosio ALB, Dias SMG (2023) Molecular mechanism of glutaminase activation through filamentation and the role of filaments in mitophagy protection. Nat Struct Mol Biol. 30(12):1902-1912.
Fromm SA, O'Connor KM, Purdy M, Bhatt PR, Loughran G, Atkins JF, Jomaa A, Mattei S (2023) The translating bacterial ribosome at 1.55 Å resolution generated by cryo-EM imaging services. Nat Commun. 14(1):1095.
Gemin O, Gluc M, Purdy M, Rosa H, Niemann M, Peskova Y, Mattei S, Jomaa A (2023) Hibernating ribosomes tether to mitochondria as an adaptive response to cellular stress during glucose depletion. bioRxiv. [Preprint]https://doi.org/10.1101/2023.10.08.561365.
Bykov YS, Flohr T, Boos F, Zung N, Herrmann JM, Schuldiner M (2022) Widespread use of unconventional targeting signals in mitochondrial ribosome proteins. EMBO J. 41(1):e109519.
Dahan N, Bykov YS, Boydston EA, Fadel A, Gazi Z, Hochberg-Laufer H, Martenson J, Denic V, Shav-Tal Y, Weissman JS, Aviram N, Zalckvar E, Schuldiner M (2022) Peroxisome function relies on organelle-associated mRNA translation. Sci Adv. 8(2):eabk2141.
Backes S, Bykov YS, Flohr T, Räschle M, Zhou J, Lenhard S, Krämer L, Mühlhaus T, Bibi C, Jann C, Smith JD, Steinmetz LM, Rapaport D, Storchová Z, Schuldiner M, Boos F, Herrmann JM (2021) The chaperone-binding activity of the mitochondrial surface receptor Tom70 protects the cytosol against mitoprotein-induced stress. Cell Rep. 35(1):108936.
Lee JH, Jomaa A, Chung S, Hwang Fu YH, Qian R, Sun X, Hsieh HH, Chandrasekar S, Bi X, Mattei S, Boehringer D, Weiss S, Ban N, Shan SO (2021) Receptor compaction and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER. Sci Adv. 7(21):eabg0942.
Zila V, Margiotta E, Turoňová B, Müller TG, Zimmerli CE, Mattei S, Allegretti M, Börner K, Rada J, Müller B, Lusic M, Kräusslich HG, Beck M (2021) Cone-shaped HIV-1 capsids are transported through intact nuclear pores. Cell. 184(4):1032-1046.e18.
Bykov YS, Rapaport D, Herrmann JM, Schuldiner M (2020) Cytosolic events in the biogenesis of mitochondrial proteins. Trends Biochem Sci. 45(8):650-667.
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