Mito-Nuclear Interaction Effects

Our research in this area mainly relates to mitochondrial malfunction, leading to disease in humans and animals, including myopathies, neuropathies, metabolic diseases, and infertility. Substantial evidence suggests it may not always be the faulty mitochondria per se that cause the disease but that it might be caused by a disrupted interaction/ communication/ signalling between the mitochondria and the nucleus. Some nuclear backgrounds seem to cope just fine with faulty mitochondrial mutations – a challenge to the medical paradigm that mito diseases arise when mutated mitochondria exceed 60% of the cellular population. We have developed experimental systems, so-called Drosophila mitolines, that allow us to quantify the health and fitness effects of different pairings of mitochondrial and nuclear genomes. The resulting data have substantial bearing on the recently introduced mitochondrial replacement therapy, where nuclear DNA is placed into unrelated mitochondrial surroundings.

The main approach to mito diseases is to alter metabolism by dietary interventions. Recently we have, therefore, extended our work to cover such effects. This complicates the issue because we found that dietary fat and amino acids differentially affect mito-nuclear interactions, in collaboration with revious Dresden Junior Fellow Dr Adam Dobson, Univ Glasgow.

See our publications on this topic:

Vaught RC, Voigt S, Dobler R, Clancy DJ, Reinhardt K, Dowling DK. 2020. Interactions between cytoplasmic and nuclear genomes confer sex‐specific effects on lifespan in Drosophila melanogaster. Journal of evolutionary biology, 33: 694-713. Link

Dobler R, Dowling DK, Morrow EH & Reinhardt K. 2018. A systematic review and meta-analysis reveals pervasive effects of germline mitochondrial replacement on components of health. Human Reproductive Update. Link

Grunau C, Voigt S, Dobler R, Dowling DK, Reinhardt K. 2018. The cytoplasm affects the epigenome in Drosophila melanogaster. Epigenomes. Link

Morrow EH, Reinhardt K, Wolff J, Dowling DK. 2015. Risks inherent to mitochondrial replacement. EMBO Reports. link to pdf

Dobler et al. 2014. A meta-analysis of the strength and nature of cytoplasmic genetic effects. Journal of Evolutionary Biology 27: 2021-2034. link to pdf.

Reinhardt et al. 2013. Mitochondria replacement, Evolution, and the Clinic. Science 341: 1345-1346. link to pdf

Here is some coverage. Note, that not everyone is happy with our conclusions: