Project 11:
Early steps in the biogenesis of mitochondrial inner membrane proteins: The role of cytosolic factors in synthesis, targeting and quality control
Johannes M. Herrmann
E-Mail: hannes.herrmann@biologie.uni-kl.de
Phone: +49 621-2052406
Cell Biology
Rhineland-Palatinate Technical University of Kaiserslautern-Landau (RPTU)
Stefan Pfeffer
E-Mail: s.pfeffer@zmbh.uni-heidelberg.de
Phone: +49 6221-546893
Zentrum für Molekulare Biologie (ZMBH)
Heidelberg University
Konstanze F. Winklhofer
E-Mail: konstanze.winklhofer@rub.de
Phone: +49 234-3228428
Molecular Cell Biology
Ruhr University Bochum
Abstract
Mitochondria consist of hundreds of proteins which are synthesized as precursors in the cytosol and imported into mitochondria mostly post-translationally. An exception from that rule are stop-anchor proteins, a class of inner membrane proteins that are imported already during their synthesis to allow passage of large domains destined for the intermembrane space across the outer mitochondrial membrane. In this project, we will dissect import and quality control mechanisms of stop-anchor proteins and elucidate which cytosolic factors are required for these processes.
Project-relevant publications
Koch C, Lenhard S, Räschle M, Prescianotto-Baschong C, Spang A, Herrmann JM (2024) The ER-SURF pathway uses ER-mitochondria contact sites for protein targeting to mitochondria. EMBO Rep. 25(4):2071-2096.
Furthmann N, Bader V, Angersbach L, Blusch A, Goel S, Sánchez-Vicente A, Krause LJ, Chaban SA, Grover P, Trinkaus VA, van Well EM, Jaugstetter M, Tschulik K, Damgaard RB, Saft C, Ellrichmann G, Gold R, Koch A, Englert B, Westenberger A, Klein C, Jungbluth L, Sachse C, Behrends C, Glatzel M, Hartl FU, Nakamura K, Christine CW, Huang EJ, Tatzelt J, Winklhofer KF (2023) NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62. Nat Commun. 14(1):8368.
Groh C, Haberkant P, Stein F, Filbeck S, Pfeffer S, Savitski MM, Boos F, Herrmann JM (2023) Mitochondrial dysfunction rapidly modulates the abundance and thermal stability of cellular proteins. Life Sci Alliance. 6(6):e202201805.
Lenhard S, Gerlich S, Khan A, Rödl S, Bökenkamp JE, Peker E, Zarges C, Faust J, Storchova Z, Räschle M, Riemer J, Herrmann JM (2023) The Orf9b protein of SARS-CoV-2 modulates mitochondrial protein biogenesis. J Cell Biol. 222(10):e202303002.
Cerullo F, Filbeck S, Patil PR, Hung HC, Xu H, Vornberger J, Hofer FW, Schmitt J, Kramer G, Bukau B, Hofmann K, Pfeffer S, Joazeiro CAP (2022) Bacterial ribosome collision sensing by a MutS DNA repair ATPase paralogue. Nature. 603(7901):509-514.
Wu Z, Berlemann LA, Bader V, Sehr DA, Dawin E, Covallero A, Meschede J, Angersbach L, Showkat C, Michaelis JB, Münch C, Rieger B, Namgaladze D, Herrera MG, Fiesel FC, Springer W, Mendes M, Stepien J, Barkovits K, Marcus K, Sickmann A, Dittmar G, Busch KB, Riedel D, Brini M, Tatzelt J, Cali T, Winklhofer KF (2022) LUBAC assembles a ubiquitin signaling platform at mitochondria for signal amplification and transport of NF-κB to the nucleus. EMBO J. 41(24):e112006.
Filbeck S, Cerullo F, Paternoga H, Tsaprailis G, Joazeiro CAP, Pfeffer S (2021) Mimicry of canonical translation elongation underlies alanine tail synthesis in RQC. Mol Cell. 81(1):104-114.e6.
Schlagowski AM, Knöringer K, Morlot S, Sánchez Vicente A, Flohr T, Krämer L, Boos F, Khalid N, Ahmed S, Schramm J, Murschall LM, Haberkant P, Stein F, Riemer J, Westermann B, Braun RJ, Winklhofer KF, Charvin G, Herrmann JM (2021) Increased levels of mitochondrial import factor Mia40 prevent the aggregation of polyQ proteins in the cytosol. EMBO J. 40(16):e107913.
Song J, Herrmann JM, Becker T (2021) Quality control of the mitochondrial proteome. Nat Rev Mol Cell Biol. 22(1):54-70.
Boos F, Krämer L, Groh C, Jung F, Haberkant P, Stein F, Wollweber F, Gackstatter A, Zöller E, van der Laan M, Savitski MM, Benes V, Herrmann JM (2019) Mitochondrial protein-induced stress triggers a global adaptive transcriptional programme. Nat Cell Biol. 21(4):442-451.
van Well EM, Bader V, Patra M, Sánchez-Vicente A, Meschede J, Furthmann N, Schnack C, Blusch A, Longworth J, Petrasch-Parwez E, Mori K, Arzberger T, Trümbach D, Angersbach L, Showkat C, Sehr DA, Berlemann LA, Goldmann P, Clement AM, Behl C, Woerner AC, Saft C, Wurst W, Haass C, Ellrichmann G, Gold R, Dittmar G, Hipp MS, Hartl FU, Tatzelt J, Winklhofer KF (2019) A protein quality control pathway regulated by linear ubiquitination. EMBO J. 38(9):e100730.
Braunger K, Pfeffer S, Shrimal S, Gilmore R, Berninghausen O, Mandon EC, Becker T, Förster F, Beckmann R (2018) Structural basis for coupling protein transport and N-glycosylation at the mammalian endoplasmic reticulum. Science. 360(6385):215-219.
Delarue M, Brittingham GP, Pfeffer S, Surovtsev IV, Pinglay S, Kennedy KJ, Schaffer M, Gutierrez JI, Sang D, Poterewicz G, Chung JK, Plitzko JM, Groves JT, Jacobs-Wagner C, Engel BD, Holt LJ (2018) mTORC1 Controls Phase Separation and the Biophysical Properties of the Cytoplasm by Tuning Crowding. Cell. 174(2):338-349.e20.
Pfeffer S, Woellhaf MW, Herrmann JM, Förster F (2015) Organization of the mitochondrial translation machinery studied in situ by cryoelectron tomography. Nat Commun. 6:6019.
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