Research Group Leader - Angelika Harbauer
Local Mechanisms Governing Mitochondrial Health in Neurons
starting Sept 2019: Max Planck research group leader at the Max Planck Institute of Neurobiology, Munich, Germany
2015 - 2019: Postdoctoral research fellow at F.M. Kirby Center for Neurobiology, Harvard Medical School and Boston Children’s Hospital, Boston, USA
2009 - 2014: Ph.D. at the Institute for Biochemistry and Molecular Biology at Albert-Ludwigs-University Freiburg, Germany
2003 - 2009: Diploma in Molecular Medicine, Albert-Ludwigs-University Freiburg, Germany and Vrije Universiteit Amsterdam, the Netherlands
The large size of neurons provides additional challenges for mitochondrial quality control, as the organelle is transported all over the axonal arbor and needs to function far away from the cell body and the bulk of the protein synthesis machinery. Local translation of mitochondrial proteins may alleviate some of this strain, yet mechanisms for mRNA transport and local protein synthesis have not been described for mitochondrial transcripts. Using mRNA live-imaging we observed mitochondrial localization of transcript encoding PTEN-induced kinase 1 (PINK1), a mitochondrial kinase important for mitophagy and mutated in hereditary forms of Parkinson’s disease. This neuron-specific mechanism ensures the local supply of freshly synthesized PINK1 to axonal mitochondria, allowing the removal of potentially hazardous organelles. Current research is focused on the extent of this mechanism of transport, which may be a fundamentally new paradigm of RNA transport and local mitochondrial biogenesis, allowing alterations of the mitochondrial proteome according to the local signaling environment. We aim to discover the underlying mechanisms that regulate local translation of mitochondrial proteins and to analyze the adaption of this important organelle in response to neuronal activity. A decline in mitochondrial health is a hallmark of many neurodegenerative disorders and aging, so understanding the molecular mechanisms that govern mitochondrial health and functions in neurons will lead to treatments and therapies that increase the healthy life span in elderly people.
List of Publications:
Harbauer A.B. , Ordonez M., Cai Z., Ashrafi G., Cartoni R., Brommer B., He Z., Schwarz T.L. (2019) PINK1 mRNA is transported with mitochondria and translated locally to support axonal mitophagy. Manuscript in preparation.
Kravic B., Harbauer A.B., Romanello V., Simeone L., Vögtle F.-N., Kaiser T., Straubinger M., Huraskin D. Böttcher M., Cerqua C., Martin E. D., Poveda-Huertes D., Buttgereit A., Rabalski A. J., Heuss, D., Rudolf R., Friedrich, O., Litchfield D., Marber M., Salviati L., Mougiakakos D., Neuhuber W., Sandri M., Meisinger C., Hashemolhosseini S. (2018) In mammalian skeletal muscle, phosphorylation of TOMM22 by protein kinase CSNK2/CK2 controls mitophagy. Autophagy, 14(2), 311-335.
Harbauer A.B. (2017) Mitochondrial health maintenance in axons. Biochem. Soc. Trans. 45, 1045–1052.
Harbauer, A.B., Opalińska, M., Herman, J.S., Rao, S., Guiard, B., Schmidt, O., Pfanner, N., and Meisinger, C. (2014) Cell cycle-dependent regulation of mitochondrial preprotein translocase. Science, 346(6213), 1109–13.
• Highlighted as Editor’s Choice
• accompanied by a Perspective by Schulz and Rehling, Science 2014 Vol. 346, Issue 6213, pp. 1059-1060.
Harbauer, A.B., Zahedi, R.P., Sickmann, A., Pfanner, N., and Meisinger, C. (2014) The Protein Import Machinery of Mitochondria: a Regulatory Hub in Metabolism, Stress and Disease. Cell Metabolism, 19, 357–372.
Gerbeth, C.*, Schmidt, O.*, Rao, S., Harbauer, A.B., Mikropoulou, D., Opalińska, M., et al. (2013). Glucose-Induced Regulation of Protein Import Receptor Tom22 by Cytosolic and Mitochondria-Bound Kinases. Cell Metabolism, 18, 578–587. (*equal contribution)
Rao, S., Schmidt, O., Harbauer, A.B., Schönfisch, B., Guiard, B., Pfanner, N., and Meisinger, C. (2012). Biogenesis of the preprotein translocase of the outer mitochondrial membrane: protein kinase A phosphorylates the precursor of Tom40 and impairs its import. Molecular Biology of the Cell 23, 1618–1627.
Rao, S.*, Gerbeth, C.*, Harbauer, A.B., Mikropoulou, D., Meisinger, C., and Schmidt, O. (2011). Signaling at the gate: Phosphorylation of the mitochondrial protein import machinery. Cell Cycle 10, 2083-2090. (*equal contribution)
Schmidt, O.*, Harbauer, A.B.*, Rao, S., Eyrich, B., Zahedi, R.P., Stojanovski, D., Schönfisch, B., Guiard, B., Sickmann, A., Pfanner, N., and Meisinger, C. (2011). Regulation of mitochondrial protein import by cytosolic kinases. Cell 144, 227-239. (*equal contribution)