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A06 | The role of mitochondrial dynamics in mtDNA maintenance

Nils-Göran Larsson
since 2019: Karolinska Institutet, Stockholm, Sweden
LARSSON Lab

Max Planck Institute for Biology of Ageing, Cologne
LARSSON group at the MPI AGE
The project was completed by the end of December 2019.


Abstract

Fundamental principles for the organisation, distribution and maintenance of mtDNA in mammalian cells are poorly understood, despite the huge impact of altered mtDNA expression on mitochondrial and age-associated diseases. We will investigate how impaired mitochondrial outer membrane fusion affects nucleoid distribution and mtDNA mutation complementation. Furthermore, we will define nucleoid protein components in mouse tissues in vivo in conditions with altered mtDNA expression.

Project-related publications

Silva Ramos, E., Motori, E., Brüser, C., Kühl, I., Yeroslaviz, A., Ruzzenente, B., Kauppila, J.H.K., Busch, J.D., Hultenby, K., Habermann, B.H., Jakobs, S., Larsson, N.G., and Mourier, A. (2019). Mitochondrial fusion is required for regulation of mitochondrial DNA replication. PLoS Genet. 15, e1008085.

Bonekamp, N.A., and Larsson, N.G. (2018). SnapShot: Mitochondrial Nucleoid. Cell 172, 388-388.e1.

Jiang, M., Kauppila, T.E.S., Motori, E., Li, X., Atanassov, I., Folz-Donahue, K., Bonekamp, N.A., Albarran-Gutierrez, S., Stewart, J.B., and Larsson, N.G. (2017). Increased total mtDNA copy number cures male infertility despite unaltered mtDNA mutation load. Cell Metab. 26, 429-436.e4.

Kukat, C., Davies, K.M., Wurm, C.A., Spåhr, H., Bonekamp, N.A., Kühl, I., Joos, F., Polosa, P.L., Park, C.B., Posse, V., Falkenberg, M., Jakobs, S., Kühlbrandt, W., and Larsson, N.G. (2015). Cross-strand binding of TFAM to a single mtDNA molecule forms the mitochondrial nucleoid. Proc. Natl. Acad. Sci. U. S. A. 112, 11288-11293.