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Mechanisms and regulation of transcription termination in human mitochondria



Mitochondria are required to convert food into usable energy forms and every cell contains thousands of them. Unlike most other cellular compartments, mitochondria have their own genomes (mtDNA) that in mammals encode for 13 of the about 90 proteins present in the respiratory chain. The existence of a separate mtDNA genome is explained by the widely accepted endosymbiotic theory, according to which the mitochondrion developed from an α-proteobacterium. During the course of time, ancestral bacterial genes have been transferred from the mitochondrial to the nuclear genome, which explains why all proteins necessary for mtDNA replication, as well as transcription and translation of mtDNA genes, are encoded in the nucleus. Mutations in nuclear-encoded proteins required for mtDNA maintenance are an important cause of neurodegeneration and muscle diseases. Mitochondrial dysfunction is also associated with common age-associated diseases (e.g. diabetes mellitus type II and Parkinson disease).

In the laboratory we are investigating the basic mechanisms of human mtDNA replication and how this process is regulated. In addition, we address the functional consequences of disease-causing mutations in genes required for mtDNA maintenance. Much of the work is performed using in vitro biochemistry and reconstituted systems for mammalian mtDNA replication, using different types of artificial templates and recombinant proteins.

Latest Publications

Uhler JP, Thörn C, Nicholls TJ, Matic S, Milenkovic D, Gustafsson CM, Falkenberg M. (2016) MGME1 processes flaps into ligatable nicks in concert with DNA polymerase γ during mtDNA replication. Nucleic Acids Res. 44(12):5861-71. doi: 10.1093/nar/gkw468. Epub 2016 May 24.

Jemt E, Persson Ö, Shi Y, Mehmedovic M, Uhler JP, Dávila López M, Freyer C, Gustafsson CM, Samuelsson T, Falkenberg M. (2015) Regulation of DNA replication at the end of the mitochondrial D-loop involves the helicase TWINKLE and a conserved sequence element. Nucleic Acids Res. 43(19):9262-75. doi: 10.1093/nar/gkv804. Epub 2015 Aug 7.

Macao B, Uhler JP, Siibak T, Zhu X, Shi Y, Sheng W, Olsson M, Stewart JB, Gustafsson CM, Falkenberg M. (2015) The exonuclease activity of DNA polymerase γ is required for ligation during mitochondrial DNA replication. Nat Commun. 2015 Jun 22;6:7303. doi: 10.1038/ncomms8303.



Prof. Dr. Maria Falkenberg

Institute of Biomedicine, University of Gothenburg

Medicinaregatan 9A
41390 Gothenburg, Sweden

Telephone +46-31-786-3444
E-mail maria.falkenberg(at)