November 27, 2019

expert reaction to study looking at mitochondrial disease in fruit flies

Research, published in Current Biology, reports that a protein has been identified in fruit flies that can be targeted to reverse the effects of disease-causing mutations in mitochondrial genes.

Prof Doug Turnbull FRS, Director of the Wellcome Centre for Mitochondrial Research, and Professor of Neurology, Newcastle University, said:

“This is fascinating research looking at nuclear factors that affect transmission of mitochondrial DNA mutations in fruit flies.  In humans, different mitochondrial DNA mutations behave differently in terms of transmission but it will be fascinating to see whether this protein is also important.  Understanding the mechanism involved might give insight into which mitochondrial DNA mutations may be most affected.”

Dr David Clancy, Lecturer, Lancaster University, said:

Does the press release accurately reflect the science?

“Fairly well, yes.

Is this good quality research?  Are the conclusions backed up by solid data?

“Yes, very good.

How does this work fit with the existing evidence?

“It is quite novel.

Have the authors accounted for confounders?  Are there important limitations to be aware of?

“The response to the technique was variable, so it didn’t always work.  The authors generally acknowledge these (and other – see below) limitations.

What are the implications in the real world?  Is there any overspeculation?

“It would be a stretch to say this study is relevant or applicable to humans – they have used one model heteroplasmic system where one of the two mitochondrial types is from another species and so this won’t necessarily apply to human disease-causing mitochondrial heteroplasmies.  (Normally cells contain mitochondrial DNA of only one type or sequence.  Heteroplasmy occurs if there is more than one type present.  It is not rare and generally benign.  In the case of mitochondrial genetic disease there tends to be heteroplasmy where one of the mtDNA types is mutated such that it causes disease.)

“I think that treatments which have their basis in this interesting discovery are either a long way off or not possible, especially because I suspect they would need to be done in developing embryos and there is the great danger of off-target effects.”

‘A genome-wide screen reveals that reducing mitochondrial DNA polymerase can promote elimination of deleterious mitochondrial mutations’ by Ason C-Y Chiang et al. was published in Current Biology at 16:00 UK time on Wednesday 27 November 2019.

DOI: 10.1016/j.cub.2019.10.060

Declared interests

Dr David Clancy: “No interests to declare.”

None others received.