Nora Voegtle
ZMBH Research Group Leader
ZMBH
Im Neuenheimer Feld 345
69120 Heidelberg, Germany
Tel. +49 (0) 6221 - 54 6866
n.voegtle@zmbh.uni-heidelberg.de
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Welcome to the future Voegtle lab!
Mitochondria are essential organelles well known for their role in ATP synthesis, multiple metabolic pathways or programmed cell death. They form a dynamic elongated network and are integrated into the cellular signalling network. To fulfill their various functions mitochondria have to build and maintain a complex proteome of more than 1000 different proteins. The vast majority of these mitochondrial proteins is imported post-translationally into the organelle and requires proteolytic processing to mature into functional and stable proteins. We are interested in the proteases that perform this processing and subsequent quality control of the incoming precursors. Maintenance of the mitochondrial proteome can also be challenged by stress or disease mutations and the cell protects mitochondrial proteostasis by eliciting transcriptionally responses ("mitochondrial unfolded protein response"). We are investigating how disease mutations affect mitochondrial proteostasis, how the cell is sensing these imbalances and how mitochondria are molecularly remodeled to cope with and overcome stress in form of toxic protein aggregates.
Selected publications Original Research Papers Kücükköse, C., Taskin, A.A., Marada, A., Brummer, T., Dennerlein, S., and Vögtle, F.N. (2021). Functional coupling of presequence processing and degradation in human mitochondria. FEBS J., 288, 600-613. Poveda-Huertes, D., Matic, S., Marada, A., Habernig, L., Licheva, M., Myketin, L., Gilsbach, R., Tosal-Castano, S., Papinski, D., Mulica, P., Kretz, O., Kücükköse, C., Taskin, A.A., Hein, L., Kraft. C., Büttner, S., Meisinger, C., and Vögtle, F.N. (2020). An early mtUPR: Redistribution of the nuclear transcription factor Rox1 into mitochondria protects against intramitochondrial proteotoxic aggregates. Mol. Cell 77, 180-188. Vögtle, F.N.#,*, Brändl, B.*, Larson, A.*, Pendziwiat, M.*, Friederich, M.W.*, White, S.M., Basinger, A., Kücükköse, C., Muhle, H., Jähn, J.A., Keminer, O., Helbig, K.L., Delto, C.F., Myketin, L., Mossmann, D., Burger, N., Miyake, N., Burnett, A., van Baalen, A., Lovell, M.A., Matsumoto, N., Walsh, M., Yu, H.C., Shinde, D.N., Stephani, U., Van Hove, J.L.K., Müller, F.J., Helbig, I.# (2018). Mutations in PMPCB Encoding the Catalytic Subunit of the Mitochondrial Presequence Protease Cause Neurodegeneration in Early Childhood. Am. J. Hum. Genet. 102, 557-573. Vögtle, F.N.*, Burkhart, J.M.*, Gonczarowska-Jorge, H., Kücükköse, C., Taskin, A.A., Kopczynski, D., Ahrends, R., Mossmann, D., Sickmann, A., Zahedi, R.P., and Meisinger, C. (2017). Landscape of submitochondrial protein distribution. Nat. Commun. 8, 290. Taskin, A.A., Kücükköse, C., Burger, N., Mossmann, D., Meisinger, C., and Vögtle, F.N. (2017). The novel mitochondrial matrix protease Ste23 is required for efficient presequence degradation and processing. Mol. Biol. Cell 28, 997-1002. Eldomery, M.K.*, Akdemir, Z.C.*, Vögtle, F.N.*, Charng, W.L., Mulica, P., Rosenfeld, J.A., Gambin, T., Gu, S., Burrage, L.C., Al Shamsi, A., Penney, S., Jhangiani, S.N., Zimmerman, H.H., Muzny, D.M., Wang, X., Tang, J., Medikonda, R., Ramachandran, P.V., Wong, L.J., Boerwinkle, E., Gibbs, R.A., Eng, C.M., Lalani, S.R., Hertecant, J., Rodenburg, R.J., Abdul-Rahman, O.A., Yang, Y., Xia, F., Wang, M.C., Lupski, J.R., Meisinger, C., and Sutton, V.R. (2016). MIPEP recessive variants cause a syndrome of left ventricular non-compaction, hypotonia, and infantile death. Genome Med. 8, 106. Burkhart, J.M., Taskin, A.A., Zahedi, R.P.#, and Vögtle, F.N.# (2015). Quantitative profiling for substrates of the mitochondrial presequence processing protease reveals candidates of a proteotoxic stress response. J. Proteome Res. 14, 4550-4563. Vögtle, F.N.#, Keller, M., Taskin, A.A., Horvath, S.E., Guan, X.L., Prinz, C., Opali?ska, M., Zorzin, C., van der Laan, M., Wenk, M.R., Schubert, R., Wiedemann, N., Holzer, M., and Meisinger, C.# (2015). Mitochondrial dynamics: The fusogenic lipid phosphatidic acid promotes the biogenesis of mitochondrial outer membrane protein Ugo1. J. Cell Biol. 210, 951-960. Mossmann, D.*, Vögtle, F.N.*, Taskin, A.A., Teixeira, P.F., Ring, J., Burkhart, J.M., Burger, N., Pinho, C.M., Tadic, J., Loreth, D., Graff, C., Metzger, F., Sickmann, A., Kretz, O., Wiedemann, N., Zahedi, R.P., Madeo, F., Glaser, E., and Meisinger, C. (2014). Amyloid-b peptide induces mitochondrial dysfunction by inhibition of preprotein maturation. Cell Metab. 20, 662-669. Vögtle, F.N.*, Wortelkamp, S.*, Zahedi, R.P., Becker, D., Leidhold, C., Gevaert, K., Kellermann, J., Voos, W., Sickmann, A., Pfanner, N., and Meisinger C. (2009). Global analysis of the mitochondrial N-Proteome identifies a processing peptidase critical for protein stability. Cell 139, 428-439.
Review Articles Gomez-Fabra Gala, M, and Vögtle, F.N. (2021). Mitochondrial proteases in human diseases. FEBS Lett. published online. Vögtle, F.N. Open questions on the mitochondrial unfolded protein response. Viewpoint, FEBS J. published online. Poveda-Huertes, D., Mulica, P., and Vögtle, F.N. (2017). The versatility of the mitochondrial presequence processing machinery: cleavage, quality control and turnover. Cell Tissue Res. 367, 73-81.
* equal contribution# corresponding author
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