Is there plasticity in mitochondrial cristae density with endurance training?

We have with interest read the paper by Nielsen and colleagues, in which the plasticity of the mitochondrial cristae is studied (Nielsen et al. 2017). The study is detailed and sophisticated and it represents a massive amount of work. The authors write: ‘We hypothesize that the mitochondrial cristae density is plastic due to endurance training’, and they conclude: ‘In the present study, we confirm this hypothesis by showing that, in human skeletal muscle, and in contrast to the current view, the mitochondrial cristae density is not constant but, instead, exhibits plasticity with long‐term endurance training.’ With all respect, we believe that the hypothesis is based upon false premises and that the conclusion is not supported by the data.

Nielsen and colleagues build their hypothesis on three previously published studies (Pesta et al. 2011; Jacobs & Lundby, 2013; Boushel et al. 2014) supposedly showing that endurance training results in higher respiration rate per mitochondrion. Unfortunately, none of these are suitable in this respect. Firstly, the study by Jacobs & Lundby (2013) concludes that training induces an increase in intrinsic mitochondrial respiratory capacity. However, the data do not support that conclusion, which is based upon Fig. 3B of Jacobs & Lundby (2013), because simple calculation from data provided in Figs 2 and 3A of Jacobs & Lundby (2013) clearly show that there are no differences in intrinsic mitochondrial respiratory capacity following training. Secondly, Pesta et al. (2011) show a training‐induced increase of mitochondrial respiratory capacity with no differences in mitochondrial content. However, mitochondrial content was evaluated by mtDNA (Pesta et al. 2011), which some of the authors in Nielsen et al. (2017) themselves have shown to be a very poor marker for mitochondrial content (Larsen et al. 2012). Thirdly, the paper by Boushel et al. (2014) is referenced to support the concept, and in this study arm muscles are used. However, Boushel and colleagues actually report no differences in the mitochondrial respiratory rates in the deltoid muscle after the training intervention, and data on mitochondrial content are not reported.

Thus, the supposed training‐induced increase in mitochondrial intrinsic respiratory capacity which should support the hypothesis of plasticity in the mitochondrial cristae density is, in our opinion, not valid.

In order to test the hypothesis, Nielsen et al. (2017) conducted a cross‐sectional study and a small, longitudinal training study. The studies are based upon human muscle biopsies originating from previously published studies comprising individuals representing a wide range of maximal oxygen uptake rates. The longitudinal training study includes muscle biopsies from obese patients with or without type 2 diabetes, pre‐ and post‐10 weeks’ training. The cross‐sectional study includes young, recreationally active soccer players and elite cross‐country skiers as well as middle aged sedentary obese and obese with type 2 diabetes. In the cross‐sectional study, a significant difference in cristae density between the groups was shown, but in the longitudinal training study no difference was found despite an increase in mitochondrial volume density and maximal oxygen uptake indicating that the mitochondrial cristae are not plastic to endurance training (Nielsen et al. 2010). In our opinion, significant differences in a cross‐sectional study and no difference in a longitudinal study cannot justify the conclusion that endurance training induces a plasticity in cristae density. Obviously, differences between groups in a cross‐sectional study is not proof of a cause–effect relationship.

In the final paragraph, the authors writes: ‘Our data unequivocally demonstrate that human skeletal muscle mitochondrial cristae density varies between populations with different physical activity levels.’ This conclusion is correct, but this is very different from what is concluded in the abstract. Moreover it is not an answer to the hypothesis the authors have put forward in the manuscript.

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Competing interests

The Authors declare that they have no competing interests.