Detection of tRNA processing faults as a screen for deleterious mt-tRNA mutations

Research

Genome Evolution and Ageing

Since the 1970's the involvement of mitochondria in the ageing process has been recognized. As we age, there is clear evidence of the accumulation of a mosaic pattern cell from different tissues that are deficient in the enzymatic capacity of the mitochondrial respiratory chain. Much of the research attention has focused on either the action of radical oxygen species, or the accumulation of somatic mutations and/or chromosomal rearrangements in mitochondrial DNA and their physiological effects. However, new hypotheses on the unusual evolutionary balance between the nuclear and mitochondrial genome are being investigated, which may have implication on the ageing process.

Latest Publications

Kauppila JHK, Baines BL, Bratic A, Simard M-L, Freyer C, Mourier A, Stamp C, Filograna R, Larsson NG, Greaver LC, Stewart JB (2016) A phenotype-driven approach to generate mouse models with pathogenic mtDNA mutations causing mitochondrial disease. Cell Reports. 16(11):2980-2990.

Stewart J.B., Alaei-Mahabadi B., Radhakrishnan S., Samuelsson T., Gorodkin J., Gustafsson C.M.,  Larsson E. (2015) Simultaneous DNA and RNA mapping of somatic mitochondrial mutations across diverse human cancers. PLoS Genetics. 11(6): e1005333.

Ross JM, Stewart JB, Hagström E, Brené S, Mourier A, Coppotelli G, Freyer C, Lagouge M, Hoffer BJ, Olson L, Larsson NG. (2013) Germline mitochondrial DNA mutations aggravate ageing and can impair brain development. Nature 501(7467):412-5. doi: 10.1038/nature12474. Epub 2013 Aug 21.