This study did not assess adrenal steroids, but steroid hormone abnormalities are fully consistent with our hypothesis and findings. Mitochondria are directly involved in production and regulation of corticosteroids including aldosterone, as has long been recognized1-4. Indeed, enzymes required for adrenal steroid hormone production are located in the mitochondria, which are involvedin both basal and stimulated adrenal hormone secretion5-8. And, adrenal steroid hormone dysregulation (including hypo and hyperadrenal manifestations) is a recognized manifestation in mitochondrial dysfunction9.

(A discussion of our proposed pathway that extends to adrenal hormone effects, among numerous other processes that may participate in a more detailed causal pathway, is in the submitted manuscript for our coenzyme Q10 randomized trial findings, with publication expected later this year. Note that the Figure 1 legend expressly designates the mechanistic model shown as an abridged version.)

Feedback and feedforward processes of products on production mechanisms10 are biologically common, and for this or other reasons, excess aldosterone can in turn inhibit or disrupt mitochondrial function11-15 with mechanisms including stimulation of mitochondrial reactive oxygen species12, 16, 17. However, that would be expected to produce the opposite of the direction effect for aldosterone that was alluded to.

We tried to find the incompletely cited “(Zange, 2013)” article, via a Pubmed search (conducted through Endnote, performed today March 30, 2014), but search terms Author=Zange + Year=2013 + Any Field= aldosterone did not yield any articles.

We did, however, identify a 2001 article with Zange as an author that did examine this:

Christ M, Zange J, Janson CP, Müller K, Kuklinski P, Schmidt BMW, Tillmann HC, Gerzer R, and Wehling M. Hypoxia modulates rapid effects of aldosterone on oxidative metabolism in human calf muscle. J Endocrinol Invest 24: 587–597, 2001.

Notably, though, this study explicitly failed to find a detectable effect of aldosterone on PCr recovery18. In discussing to time constants of PCr recovery, this article expressly states “Recovery kinetics were not significantly modified by the injection of aldosterone.” And later, “An aldosterone induced modulation of the time constant of the increase of PCr in the recovery period after isometric exercise, which is a marker of the aerobic ATP synthesis rate, cannot be detected.”

To summarize, mitochondrial are involved in production of steroid hormones, and mitochondrial dysfunction leads to alterations in steroid hormones: adrenal hormone alterations are wholly consistent with our findings. While feedforward and feedback regulation systems are common, in fact, pharmacological manipulation of aldosterone was not found to alter PCr recovery kinetics in the article we identified that examined this

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