July 6, 2016

expert reaction to a study looking at how mitochondrial and nuclear DNA matching shapes metabolism and healthy ageing

Publishing in Nature, scientists have reported that, in their study in mice, looking at mitochondrial donation, the matching of transferred mitochondrial DNA to nuclear DNA has an impact on metabolism and healthy ageing.

Prof. Doug Turnbull, Professor of Neurology, Newcastle University, said:

“This is an interesting study using highly inbred mouse strains in which there has been a transfer of mitochondrial DNA from another inbred mouse strain. The authors have carefully documented changes in metabolism due to the new mitochondrial DNA and studied these mice into older age. Interestingly, the mice with the changed mitochondrial DNA had an extended median lifespan and fewer signs of ageing.

“The relevance of this, and other studies using inbred species, to mitochondrial donation is not clear. It is important to remember that humans are highly outbred and are constantly mixing nuclear and mitochondrial genomes”

Dr Dusko Ilic, Reader in stem cell science, King’s College London, said:

“In the report a group of Spanish scientists suggest that interaction of mitochondrial and nuclear DNA shape metabolic performance of the organism, and in such a way influences healthy ageing and longevity.

“Although the hypothesis is based on a study done in two strains of highly inbred mice, the concept is still fascinating and mind-boggling. Obviously the study has to be repeated on animals that are not inbred, and species other than mice, before we can extrapolate the phenomenon to humans. At that stage we can worry whether a pre-selection of mitochondrial donor should be considered for the emerging field of preventing transmission of mitochondrial DNA disease by mitochondrial replacement therapy in human eggs.”

Prof. Robert Lightowlers, Director of the Institute for Cell and Molecular Biosciences, Newcastle University, said:

“Human mitochondrial DNA is a relatively small (approx. 16.5 thousand base pairs) genome but is surprisingly variable in sequence across the healthy population. The work published by Dr.Enriquez and his team ask the question of whether switching normal mtDNA in mice that differ in only neutral polymorphisms can cause conflict between the nuclear and mitochondrial genome.

“The authors perform a remarkable and very thorough study to determine whether such a conflict could cause any measurable physiological effects in mice. Although the genotypes varied by only a limited number of neutral polymorphisms, the effects on whole body physiology and healthy ageing was clearly measurable. Should this study influence our thinking when considering mitochondrial replacement for prospective mothers harbouring pathogenic mtDNA mutations? Clearly, the safest and most simple option is to assure the donor mtDNA genotype is as similar to the recipient genotype as possible. This study is important, as its extensive analysis shows clearly that in-bred species of mice in the laboratory show surprising susceptibility to switching even neutral mtDNA genotypes. Whether these studies can be extrapolated to the case in out-bred populations such as humans is less clear, but this work is an important contribution to the necessary and continuing debate concerning mtDNA replacement.”

* ‘Mitochondrial and nuclear DNA matching shapes metabolism and healthy ageing’ by Latorre-Pellicer et al. will be published in Nature on Wednesday 6th July.

All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/tag/mitochondrial-dna/

Declared interests

Dr Dusko Ilic: ‘I declare no conflict of interests.’

Prof. Robert Lightowlers: Professor Lightowlers is a member of the Wellcome Trust Centre for Mitochondrial Research.

Prof. Doug Turnbull: None received