Project 15:
Contributions of ubiquitin signaling to the maintenance of mitochondrial import channels
Axel Methner
E-Mail: axel.methner@gmail.com
Phone: +49 172-4510481
University Medical Center of the Johannes Gutenberg University Mainz
Helle Ulrich
E-Mail: h.ulrich@imb-mainz.de
Phone: +49 6131-3921490
Institute of Molecular Biology (IMB) & Johannes Gutenberg University Mainz
Abstract
Mitochondria are vital for energy production, metabolism, and cellular balance, and protein import is essential for their function. Mitochondria-derived vesicles (MDVs) can remove faulty import channel proteins, which preserves mitochondrial health by targeting and discarding damaged components. The ubiquitin system appears to serve as a master regulator of the process, but the mechanistic details remain poorly understood. This project aims at elucidating the ubiquitin signals controlling MDV formation and investigate their impact on protein import and the maintenance of mitochondrial function.
Project-relevant publications
Renz C, Asimaki E, Meister C, Albanèse V, Petriukov K, Krapoth NC, Wegmann S, Wollscheid HP, Wong RP, Fulzele A, Chen JX, Léon S, Ulrich HD (2024) Ubiquiton-An inducible, linkage-specific polyubiquitylation tool. Mol Cell. 84(2):386-400.e11.
Bueno D, Narayan Dey P, Schacht T, Wolf C, Wüllner V, Morpurgo E, Rojas-Charry L, Sessinghaus L, Leukel P, Sommer C, Radyushkin K, Florin L, Baumgart J, Stamm P, Daiber A, Horta G, Nardi L, Vasic V, Schmeisser MJ, Hellwig A, Oskamp A, Bauer A, Anand R, Reichert AS, Ritz S, Nocera G, Jacob C, Peper J, Silies M, Frauenknecht KBM, Schäfer MKE, Methner A (2023) NECAB2 is an endosomal protein important for striatal function. Free Radic Biol Med. 208:643-656.
Wegmann S, Meister C, Renz C, Yakoub G, Wollscheid HP, Takahashi DT, Mikicic I, Beli P, Ulrich HD (2022) Linkage reprogramming by tailor-made E3s reveals polyubiquitin chain requirements in DNA-damage bypass. Mol Cell. 82(8):1589-1602.e5.
Wolf C, Pouya A, Bitar S, Pfeiffer A, Bueno D, Rojas-Charry L, Arndt S, Gomez-Zepeda D, Tenzer S, Bello FD, Vianello C, Ritz S, Schwirz J, Dobrindt K, Peitz M, Hanschmann EM, Mencke P, Boussaad I, Silies M, Brüstle O, Giacomello M, Krüger R, Methner A (2022) GDAP1 loss of function inhibits the mitochondrial pyruvate dehydrogenase complex by altering the actin cytoskeleton. Commun Biol. 5(1):541.
Zhang L, Dietsche F, Seitaj B, Rojas-Charry L, Latchman N, Tomar D, Wüst RC, Nickel A, Frauenknecht KB, Schoser B, Schumann S, Schmeisser MJ, Vom Berg J, Buch T, Finger S, Wenzel P, Maack C, Elrod JW, Parys JB, Bultynck G, Methner A (2022) TMBIM5 loss of function alters mitochondrial matrix ion homeostasis and causes a skeletal myopathy. Life Sci Alliance. 5(10):e202201478.
Renz C, Albanèse V, Tröster V, Albert TK, Santt O, Jacobs SC, Khmelinskii A, Léon S, Ulrich HD (2020) Ubc13-Mms2 cooperates with a family of RING E3 proteins in budding yeast membrane protein sorting. J Cell Sci. 133(10):jcs244566.
Takahashi TS, Wollscheid HP, Lowther J, Ulrich HD (2020) Effects of chain length and geometry on the activation of DNA damage bypass by polyubiquitylated PCNA. Nucleic Acids Res. 48(6):3042-3052.
Connolly NMC, Theurey P, Adam-Vizi V, Bazan NG, Bernardi P, Bolaños JP, Culmsee C, Dawson VL, Deshmukh M, Duchen MR, Düssmann H, Fiskum G, Galindo MF, Hardingham GE, Hardwick JM, Jekabsons MB, Jonas EA, Jordán J, Lipton SA, Manfredi G, Mattson MP, McLaughlin B, Methner A, Murphy AN, Murphy MP, Nicholls DG, Polster BM, Pozzan T, Rizzuto R, Satrústegui J, Slack RS, Swanson RA, Swerdlow RH, Will Y, Ying Z, Joselin A, Gioran A, Moreira Pinho C, Watters O, Salvucci M, Llorente-Folch I, Park DS, Bano D, Ankarcrona M, Pizzo P, Prehn JHM (2018) Guidelines on experimental methods to assess mitochondrial dysfunction in cellular models of neurodegenerative diseases. Cell Death Differ. 25(3):542-572.
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