Maintenance and inheritance of mitochondrial DNA

Prof. Dr. Christof Osman

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+49 89 2180 74756

osman@bio.lmu.de

B02.058

LSM Speaker - Graduate School Life Science Munich

Osman-lab.de

Research

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Mitochondria convert nutrients into chemical energy and thereby enable essential processes in eukaryotic cells. To function, they rely on their own genetic material, mitochondrial DNA (mtDNA). The integrity and the correct number of these genomes in each cell are crucial for cellular health. However, how cells maintain functional mtDNA and regulate its abundance within the dynamic mitochondrial network remains only partially understood.

Our research dissects these processes to reveal fundamental principles required for mitochondrial genome stability. Because failures in mtDNA maintenance contribute to ageing and a wide range of metabolic diseases, our work provides critical insights linking basic cell biology to human health.

Methods and Approaches

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To decode the principles of mitochondrial maintenance, we utilize the budding yeast Saccharomyces cerevisiae as a sophisticated genetic model. This system allows us to manipulate mitochondrial genomes and monitor their dynamics in living cells through quantitative live-cell imaging and microfluidics. Our methodology is interdisciplinary, ranging from flow cytometry and genetic analysis to advanced proteomics and mass spectrometry. By combining these experimental approaches with computational image analysis and modeling, we obtain a quantitative understanding of how cells safeguard their genetic integrity. This environment provides students with diverse training across genetics, cell biology, and biochemistry.

Publications

Local mitochondrial physiology defined by mtDNA quality guides purifying selection (2026) Thoma, F., Hagen, J., Rathberger, R., Padovani, F., Hörl, D., Schmoller, K., Osman, C. PLOS Genetics 22(1): e1011836

Mrx6 binds the Lon protease Pim1 N-terminal domain to confer selective substrate specificity and regulate mtDNA copy number (2026) Schrott, S., Marafelli, I., Gerle, C., Bibinger, S., Bertgen, L., Marino, G., Schwenkert, S., Rathberger, R., Herrmann, J., Osman, C. Nucleic Acids Research 54(2): gkaf1390

Real-time assessment of mitochondrial DNA heteroplasmy dynamics at the single-cell level (2024) Roussou, R., Metzler, D., Padovani, F., Thoma, F., Schwarz, R., Shraiman, B., Schmoller, K., Osman, C. The EMBO Journal 43(22): 5340-5359

Two mitochondrial HMG-box proteins, Cim1 and Abf2, antagonistically regulate mtDNA copy number in Saccharomyces cerevisiae (2023) Schrott, S., Osman, C. Nucleic Acids Research 51(21): 11813-11835

Cristae-dependent quality control of the mitochondrial genome (2021) Jakubke, C.*, Roussou, R.*, Maiser, A., Schug, C., Thoma, F., Bunk, R., Hörl, D., Leonhardt, H., Walter, P., Klecker, T., Osman, C. Science Advances 7(36): eabi8886

Publication list

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