Universität zu Köln 

Dr. Tina Wenz

Institut für Genetik, Universität zu Köln
email: tina.wenz@uni-koeln.de
phone: +49-(0)221 470 8599
website

The mitochondrial oxidative phosphorylation system (OXPHOS) provides the majority of cellular ATP supply and is hence essential for cellular survival. OXPHOS derives from dual genetic origin: Both nuclear and mitochondrial (mt) DNA encode for essential structural subunits of the individual OXPHOS enzymes. Mitochondria houses a protein synthesis machinery specialised for the production of the mtDNA encoded proteins. Many aspects of mitochondrial protein synthesis are not understood. One open question is how mitochondrial protein synthesis can be regulated to ultimately modulate OXPHOS function and ATP supply. Posttranslational modifications of the main component of the mitochondrial protein synthesis machinery, the mitochondrial ribosome (mitoribosome), emerge as a possible regulatory mechanism. The mitoribosome is a target for the mitochondrial NAD+-dependent deacetylase Sirt3. Deacetylation of acetylated lysine residues results in decreased mitoribosomal activity and mitochondrial translation. The molecular basis and the physiological significance of this regulatory mechanism are so far unclear. In this project, we will analyse how deacetylation of the mitoribosome by Sirt3 regulates mitoribosomal function in vivo and how these modifications mediate the adaptation of the mitochondrial protein synthesis to changing environmental conditions and ATP demand. The proposed work will yield important insights into the impact of deacetylation of the mitoribosome in modulating mitochondrial protein synthesis and hence OXPHOS function.

Running time: 07/2011 – 06/2015

Recent publications:

Tischner, C., Hofer, A., Wulff, V., Stepek, J., Dumitru, I., Becker, L., Haack, T., Kremer, L., Datta, A.N., Sperl, W., Floss, T., Wurst, W., Chrzanowska-Lightowlers, Z., de Angelis, M.H., Klopstock, T., Prokisch, H., and Wenz, T. (2014). MTO1 mediates tissue-specificity of OXPHOS defects via tRNA modification and translation optimization, which can be bypassed by dietary intervention. Hum Mol Genet. pii: ddu743. [Epub ahead of print]

Becker, L., Kling, E., Schiller, E., Zeh, R., Schrewe, A., Hölter, S.M., Mossbrugger, I., Calzada-Wack, J., Strecker, V., Wittig, I., Dumitru, I., Wenz, T., Bender, A., Aichler, M., Janik, D., Neff, F., Walch, A., Quintanilla-Fend, L., Floss, T., Bekeredjian, R., Gailus-Durner, V., Fuchs, H., Wurst, W., Meitinger, T., Prokisch, H., de Angelis, M.H., and Klopstock, T. (2014). MTO1-deficient mouse model mirrors the human phenotype showing complex I defect and cardiomyopathy. PLoS One 9(12):e114918. PubMed

Missios, P., Zhou, Y., Guachalla, L.M., von Figura, G., Wegner, A., Chakkarappan, S.R., Binz, T., Gompf, A., Hartleben, G., Burkhalter, M.D., Wulff, V., Günes, C., Sattler, R.W., Song, Z., Illig, T., Klaus, S., Böhm, B.O., Wenz, T., Hiller, K., Rudolph, K.L. (2014). Glucose substitution prolongs maintenance of energy homeostasis and lifespan of telomere dysfunctional mice. Nat Commun. 5, 4924. PubMed

Hofer, A. and Wenz, T. (2014). Post-translational modification of mitochondria as a novel mode of regulation. Exp Gerontol. 56, 202-20. PubMed 

Koenig, S., Luheshi, G.N., Wenz, T., Gerstberger, R., Roth, J., Rummel, C. (2014). Leptin is involved in age-dependent changes in response to systemic inflammation in the rat. Brain Behav Immun. 36, 128-38. PubMed

Hofer, A., Noe, N., Tischner, C., Kladt, N., Lellek, V., Schauß, A., Wenz, T. (2014). Defining the action spectrum of potential PGC-1? activators on a mitochondrial and cellular level in vivo. Hum Mol Genet. 23(9), 2400-15. PubMed

Peralta, S., Torraco, A., Wenz, T., Garcia, S., Diaz, F., Moraes, C.T. (2014). Partial complex I deficiency due to the CNS conditional ablation of Ndufa5 results in a mild chronic encephalopathy but no increase in oxidative damage. Hum Mol Genet. 23(6), 1399-412. PubMed

Wenz, T. (2013). Regulation of mitochondrial biogenesis and PGC-1? under cellular stress. Mitochondrion. 13(2), 134-42. Review PubMed

Noe, N., Dillon, L., Lellek, V., Diaz, F., Hida, A., Moraes, C.T., and Wenz, T. (2013). Bezafibrate improves mitochondrial function in the CNS of a mouse model of mitochondrial encephalopathy. Mitochondrion. 13(5), 417-26. PubMed

Wenz, T. (2011). Mitochondria and PGC-1? in aging and age-associated diseases. J Aging Res. 2011:810619 PubMed

Wenz, T., Wang, X., Marini, M., Moraes, C.T. (2011). A metabolic shift induced by a PPAR panagonist markedly reduces the effects of pathogenic mitochondrial tRNA mutations. J Cell Mol Med. 15(11), 2317-25. PubMed 

Wenz, T., Wang, X., Marini, M., and Moraes, C.T. (2010). A metabolic shift induced by a PPAR panagonist markedly reduces the effects of pathogenic mitochondrial tRNA mutations. J. Cell. Mol. Med. 15, 2317-25.

Wenz, T., Hielscher, R., Hellwig, P., Schägger, H., and Hunte, C. (2009). Role of phospholipids in respiratory cytochrome bc1 complex catalysis and supercomplex formation. BBA Bioenerg. 6, 609-616.

Wenz, T., Rossi, S.G., Rotundo, R.L., Spiegelman, B.M., and Moraes, C.T. (2009). Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging. Proc. Natl. Acad. Sci. U.S.A. 106, 20405-10.

Wenz, T.*, Luca, C.*, Torraco, A., and Moraes, C.T. (2009). MTERF2 regulates oxidative phosphorylation by modulating mtDNA transcription. Cell Metab. 9, 499-511. (*equal contributions).

Wenz, T., Diaz, F., Hernandez, D., and Moraes, C.T. (2009). Regular exercise is protective for mice with mitochondrial myopathy. J. Appl. Phys. 106, 1712-1719.

Wenz, T., Diaz, F., Spiegelman, B., and Moraes, C.T. (2008). Activation of the PPAR/PGC-1? pathway prevents a bioenergetic deficit and effectively improves a mitochondrial myopathy phenotype. Cell Metab. 8, 249-56

Wenz, T., Covian, R., Hellwig, P., Macmillan, F., Meunier, B., Trumpower, B.L., and Hunte, C. (2007). Mutational analysis of cytochrome b at the ubiquinol oxidation site of yeast complex III. J. Biol. Chem. 282, 3977-88.

Wenz, T., Hellwig, P., MacMillan, F., Meunier, B., and Hunte, C. (2006). Probing the role of E272 in quinol oxidation of mitochondrial complex III. Biochemistry 45, 9042-9052.