Project 12:
Coordination of proteostasis and mitochondrial intermembrane space protein import
Thorsten Hoppe
E-Mail: thorsten.hoppe@uni-koeln.de
Phone: +49 221-478-84218
Institute for Genetics & CECAD, University of Cologne
Jan Riemer
E-Mail: jan.riemer@uni-koeln.de
Phone: +49 221-470-7306
Institute of Biochemistry
Faculty of Mathematics and Natural Sciences
University of Cologne
Abstract
Mitochondria import most of their ~1,500 proteins from the cytosol. Many intermembrane space (IMS) proteins lack classical targeting sequences and instead use conserved cysteine residues and hydrophobic patches for import via the disulfide relay machinery. These proteins, synthesized on cytosolic ribosomes and imported post-translationally, can accumulate in the cytosol if the relay is inactive, triggering stress responses and proteasomal degradation. The team of the Riemer and Hoppe labs will investigate these processes in C. elegans and human cells, focusing on the targeting, import, stabilization, and degradation of disulfide relay-dependent proteins. This project aims to uncover conserved mechanisms and the physiological role of the disulfide relay system, contributing valuable insights to the SPP2453 consortium.
Project-relevant publications
Charmpilas N, Sotiriou A, Axarlis K, Tavernarakis N, Hoppe T (2024) Reproductive regulation of the mitochondrial stress response in Caenorhabditis elegans. Cell Rep. 43(6):114336.
Anton V, Buntenbroich I, Simões T, Joaquim M, Müller L, Buettner R, Odenthal M, Hoppe T, Escobar-Henriques M (2023) E4 ubiquitin ligase promotes mitofusin turnover and mitochondrial stress response. Mol Cell. 83(16):2976-2990.e9.
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.
Peker E, Weiss K, Song J, Zarges C, Gerlich S, Boehm V, Trifunovic A, Langer T, Gehring NH, Becker T, Riemer J (2023) A two-step mitochondrial import pathway couples the disulfide relay with matrix complex I biogenesis. J Cell Biol. 222(7):e202210019.
Hermeling JC, Herholz M, Baumann L, Cores EC, Zečić A, Hoppe T, Riemer J, Trifunovic A (2022) Mitochondria-originated redox signalling regulates KLF-1 to promote longevity in Caenorhabditis elegans. Redox Biol. 58:102533.
Ravanelli S, Li Q, Annibal A, Trifunovic A, Antebi A, Hoppe T (2022) Reprograming of proteasomal degradation by branched chain amino acid metabolism. Aging Cell. 21(12):e13725.
Finger Y, Habich M, Gerlich S, Urbanczyk S, van de Logt E, Koch J, Schu L, Lapacz KJ, Ali M, Petrungaro C, Salscheider SL, Pichlo C, Baumann U, Mielenz D, Dengjel J, Brachvogel B, Hofmann K, Riemer J (2020) Proteasomal degradation induced by DPP9-mediated processing competes with mitochondrial protein import. EMBO J. 39(19):e103889.
Ravanelli S, den Brave F, Hoppe T (2020) Mitochondrial quality control governed by ubiquitin. Front Cell Dev Biol. 8:270.
Calabrese G, Peker E, Amponsah PS, Hoehne MN, Riemer T, Mai M, Bienert GP, Deponte M, Morgan B, Riemer J (2019) Hyperoxidation of mitochondrial peroxiredoxin limits H2O2-induced cell death in yeast. EMBO J. 38(18):e101552.
Petrungaro C, Zimmermann KM, Küttner V, Fischer M, Dengjel J, Bogeski I, Riemer J (2015) The Ca²+-dependent release of the Mia40-induced MICU1-MICU2 dimer from MCU regulates mitochondrial Ca2+ uptake. Cell Metab. 22(4):721-33.
Read more
All Projects
Find out more about the other tandem/tridem projects that are conducted as part of the SPP2453.
Scientific Background
See what is already known in the mitostasis research area and get to know the central questions of the SPP2453.
Structure
See how the Priority Program SPP2453 is organized and whom to contact if you have questions.