Project 01:
Dissecting the mechanisms linking proteasome function to mitochondrial proteostasis
Daniel Bano
E-Mail: daniel.bano@dzne.de
Phone: +49 228-43302510
Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE)
Helmholtz-Gemeinschaft, Bonn
Alexander Bartelt
E-Mail: alexander.bartelt@med.lmu.de
Phone: +49 89-4400-43905
Institute for Cardiovascular Prevention
LMU Hospital Munich
Elke Krüger
E-Mail: elke.krueger@uni-greifswald.de
Phone: +49 3834-865400
Institut für Medizinische Biochemie und Molekularbiologie
University Medicine Greifswald
Abstract
The “MITOGRADE” tridem project will assess the contribution of proteasome to the mitochondrial proteome. By employing an interdisciplinary cross-species approach, MITOGRADE will investigate the transcriptional regulation of the mitochondria-to-nucleus response upon proteasome inhibition and the downstream inflammatory pathways that are associated with inherited proteasomopathy. Importantly, our mechanistic study will define the integration of signals that assure organelle homeostasis and prevent pathogenic processes linked to aberrant mitochondrial bioenergetics.
Project-relevant publications
Jackson J, Hoffmann C, Scifo E, Wang H, Wischhof L, Piazzesi A, Mondal M, Shields H, Zhou X, Mondin M, Ryan EB, Döring H, Prehn JHM, Rottner K, Giannone G, Nicotera P, Ehninger D, Milovanovic D, Bano D (2024) Actin-nucleation promoting factor N-WASP influences alpha-synuclein condensates and pathology. Cell Death Dis. 15(4):304.
Ebstein F, Küry S, Most V, Rosenfelt C, Scott-Boyer MP, van Woerden GM, Besnard T, Papendorf JJ, Studencka-Turski M, Wang T, Hsieh TC, Golnik R, Baldridge D, Forster C, de Konink C, Teurlings SMW, Vignard V, van Jaarsveld RH, Ades L, Cogné B, Mignot C, Deb W, Jongmans MCJ, Cole FS, van den Boogaard MH, Wambach JA, Wegner DJ, Yang S, Hannig V, Brault JA, Zadeh N, Bennetts B, Keren B, Gélineau AC, Powis Z, Towne M, Bachman K, Seeley A, Beck AE, Morrison J, Westman R, Averill K, Brunet T, Haasters J, Carter MT, Osmond M, Wheeler PG, Forzano F, Mohammed S, Trakadis Y, Accogli A, Harrison R, Guo Y, Hakonarson H, Rondeau S, Baujat G, Barcia G, Feichtinger RG, Mayr JA, Preisel M, Laumonnier F, Kallinich T, Knaus A, Isidor B, Krawitz P, Völker U, Hammer E, Droit A, Eichler EE, Elgersma Y, Hildebrand PW, Bolduc F, Krüger E, Bézieau S (2023) PSMC3 proteasome subunit variants are associated with neurodevelopmental delay and type I interferon production. Sci Transl Med. 15(698):eabo3189.
Giroud M, Kotschi S, Kwon Y, Le Thuc O, Hoffmann A, Gil-Lozano M, Karbiener M, Higareda-Almaraz JC, Khani S, Tews D, Fischer-Posovszky P, Sun W, Dong H, Ghosh A, Wolfrum C, Wabitsch M, Virtanen KA, Blüher M, Nielsen S, Zeigerer A, García-Cáceres C, Scheideler M, Herzig S, Bartelt A (2023) The obesity-linked human lncRNA AATBC stimulates mitochondrial function in adipocytes. EMBO Rep. 24(10):e57600.
Koçberber Z, Willemsen N, Bartelt A (2023) The role of proteasome activators PA28αβ and PA200 in brown adipocyte differentiation and function. Front Endocrinol (Lausanne). 14:1176733.
Panagiotidou E, Gioran A, Bano D, Chondrogianni N (2023) Neuron-specific proteasome activation exerts cell non-autonomous protection against amyloid-beta (Aβ) proteotoxicity in Caenorhabditis elegans. Redox Biol. 65:102817.
Waad Sadiq Z, Brioli A, Al-Abdulla R, Çetin G, Schütt J, Murua Escobar H, Krüger E, Ebstein F (2023) Immunogenic cell death triggered by impaired deubiquitination in multiple myeloma relies on dysregulated type I interferon signaling. Front Immunol. 14:982720.
Çetin G, Studencka-Turski M, Venz S, Schormann E, Junker H, Hammer E, Völker U, Ebstein F, Krüger E (2022) Immunoproteasomes control activation of innate immune signaling and microglial function. Front Immunol. 13:982786.
Jackson J, Wischhof L, Scifo E, Pellizzer A, Wang Y, Piazzesi A, Gentile D, Siddig S, Stork M, Hopkins CE, Händler K, Weis J, Roos A, Schultze JL, Nicotera P, Ehninger D, Bano D (2022) SGPL1 stimulates VPS39 recruitment to the mitochondria in MICU1 deficient cells. Mol Metab. 61:101503.
Piazzesi A, Wang Y, Jackson J, Wischhof L, Zeisler-Diehl V, Scifo E, Oganezova I, Hoffmann T, Gómez Martín P, Bertan F, Wrobel CJJ, Schroeder FC, Ehninger D, Händler K, Schultze JL, Schreiber L, van Echten-Deckert G, Nicotera P, Bano D (2022) CEST-2.2 overexpression alters lipid metabolism and extends longevity of mitochondrial mutants. EMBO Rep. 23(5):e52606.
Willemsen N, Arigoni I, Studencka-Turski M, Krüger E, Bartelt A (2022) Proteasome dysfunction disrupts adipogenesis and induces inflammation via ATF3. Mol Metab. 62:101518.
Wischhof L, Lee HM, Tutas J, Overkott C, Tedt E, Stork M, Peitz M, Brüstle O, Ulas T, Händler K, Schultze JL, Ehninger D, Nicotera P, Salomoni P, Bano D (2022) BCL7A-containing SWI/SNF/BAF complexes modulate mitochondrial bioenergetics during neural progenitor differentiation. EMBO J. 41(23):e110595.
Wischhof L, Scifo E, Ehninger D, Bano D (2022) AIFM1 beyond cell death: An overview of this OXPHOS-inducing factor in mitochondrial diseases. EBioMedicine. 83:104231.
Bano D, Salomoni P, Ehninger D, Nicotera P (2021) The histone code in dementia: Transcriptional and chromatin plasticity fades away. Curr Opin Pharmacol. 60:117-122.
Bertan F, Wischhof L, Scifo E, Guranda M, Jackson J, Marsal-Cots A, Piazzesi A, Stork M, Peitz M, Prehn JHM, Ehninger D, Nicotera P, Bano D (2021) Comparative analysis of CI- and CIV-containing respiratory supercomplexes at single-cell resolution. Cell Rep Methods. 1(1):100002.
Scheiblich H, Dansokho C, Mercan D, Schmidt SV, Bousset L, Wischhof L, Eikens F, Odainic A, Spitzer J, Griep A, Schwartz S, Bano D, Latz E, Melki R, Heneka MT (2021) Microglia jointly degrade fibrillar alpha-synuclein cargo by distribution through tunneling nanotubes. Cell. 184(20):5089-5106.e21.
Gioran A, Piazzesi A, Bertan F, Schroer J, Wischhof L, Nicotera P, Bano D (2019) Multi-omics identify xanthine as a pro-survival metabolite for nematodes with mitochondrial dysfunction. EMBO J. 38(6):e99558.
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