B13 | Novel paradigms in the regulation of mitochondrial integrated stress responses
Aleksandra Trifunovic
CECAD Research Center/Institute for Mitochondrial Diseases and Ageing
University Hospital Cologne
E-mail: aleksandra.trifunovic
uk-koeln.de
Phone: +49 - 221 / 478 84291
For more information and contact please visit the TRIFUNOVIC LAB.
Running time within the CRC 1218: 07/2024 - 06/2028.
Abstract
Over the last few years, it became clear that one specific pathway has been activated in response to perturbation in OXPHOS activity, preceding other adaptive changes in mitochondrial biogenesis or antioxidant defence, namely the mitochondrial integrated stress response (mitoISR). We propose to further dissect this stress response by specifically investigating the regulation and consequences of acute to chronic mitoISR switch and dissecting the role of mitoISR in the regulation of postmitotic differentiation.
Within the CRC1218 Prof. Trifunovic is also a project leader of the project Z02. Click here for more information.
Recent project-related publications
Kaul H, Isermann L, Senft K, Popovic M, Georgomanolis T, Baumann L, Sivanesan P, Pouikli A, Nolte H, Lucic B, Hildebrandt X, Seidel K, Gnad T, Gaedke F, Göbel U, Peters F, Cherevatenko M, Park JH, Schauss A, Peltzer N, Brüning JC, Kornfeld JW, Pfeifer A, Langer T, Lusic M, Wickström SA, Frezza C, Trifunovic A. 2-hydroxyglutarate mediates whitening of brown adipocytes coupled to nuclear softening upon mitochondrial dysfunction. Nat Metab. 2025 Aug 1. doi: 10.1038/s42255-025-01332-8. Epub ahead of print. PMID: 40750944.
Joaquim M, Altin S, Bulimaga MB, Simões T, Nolte H, Bader V, Franchino CA, Plouzennec S, Szczepanowska K, Marchesan E, Hofmann K, Krüger M, Ziviani E, Trifunovic A, Chevrollier A, Winklhofer KF, Motori E, Odenthal M, Escobar-Henriques M. Mitofusin 2 displays fusion-independent roles in proteostasis surveillance. Nat Commun. 2025 Feb 10;16(1):1501. doi: 10.1038/s41467-025-56673-5. PMID: 39929801; PMCID: PMC11811173.
Popovic M, Isermann L, Geißen S, Senft K, Georgomanolis T, Baldus S, Frezza C, Trifunovic A. Tissue-specific adaptations to cytochrome c oxidase deficiency shape physiological outcomes. Biochim Biophys Acta Mol Basis Dis. 2024 Nov 27:167567. doi: 10.1016/j.bbadis.2024.167567. Epub ahead of print. PMID: 39613003.
Moschandrea C, Kondylis V, Evangelakos I, Herholz M, Schneider F, Schmidt C, Yang M, Ehret S, Heine M, Jaeckstein MY, Szczepanowska K, Schwarzer R, Baumann L, Bock T, Nikitopoulou E, Brodesser S, Krüger M, Frezza C, Heeren J, Trifunovic A*, Pasparakis M* (2023). Mitochondrial dysfunction abrogates dietary lipid processing in enterocytes. Nature Dec 20. DOI: 10.1038/s41586-023-06857-0. Online ahead of print. (*corresponding authors)
Croon M, Szczepanowska K, Popovic M, Lienkamp C, Senft K, Brandscheid CP, Bock T, Gnatzy-Feik L, Ashurov A, Acton RJ, Kaul H, Pujol C, Rosenkranz S, Kruger M, Trifunovic A (2022). FGF21 modulates mitochondrial stress response in cardiomyocytes only under mild mitochondrial dysfunction. Sci Adv 8:eabn7105. DOI: 10.1126/sciadv.abn7105.
Kaspar S, Oertlin C, Szczepanowska K, Kukat A, Senft K, Lucas C, Brodesser S, Hatzoglou M, Larsson O, Topisirovic I, Trifunovic A (2021). Adaptation to mitochondrial stress requires CHOP-directed tuning of ISR. Sci Adv 7. DOI: 10.1126/sciadv.abf0971.
Willenborg S, Sanin DE, Jais A, Ding X, Ulas T, Nuchel J, Popovic M, MacVicar T, Langer T, Schultze JL, Gerbaulet A, Roers A, Pearce EJ, Bruning JC, Trifunovic A, Eming SA (2021). Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing. Cell Metab 33:2398-2414 e2399. DOI: 10.1016/j.cmet.2021.10.004.