Mitochondria isolated from the striatum brain of acute paraquat treated rats exhibit a higher degree of oxidative phosphorylation coupling, which shows that they are not subject to energetic dysfunction upon acute paraquat administration

Abstract

In the recent article by Czerniczyniec et al. (2015) entitled BImpairment of striatal mitochondrial function by acute paraquat poisoning^, published in the journal J Bioenerg Biomembr 2015; 47(5): 395-408, various aspects of the bioenergetics of mitochondria isolated from the striatum and the cerebral cortex of the brain during acute paraquat toxicity have been investigated. The bioenergetic aspects studied in this investigation are basically fall into two large categories: i) the determination of the state 4 mitochondrial respiration (state 4), the state 3 mitochondrial respiration (state 3), and the respiratory control ratio (RC); and ii) the determination of the activity of mitochondrial complex I-III, mitochondrial complex II-III, and mitochondrial complex IV. On the basis of all of these results, Czerniczyniec et al. (2015) conclude the existence of a paraquat dysfunction in the bioenergetics of mitochondria isolated from the striatum of the brain. However, both a part of the methodology used and the interpretation of the above-mentioned results obtained exhibit serious fallacies and contradictions that do not support the conclusion of the authors with respect to a negative alteration of the bioenergetics of the striatum mitochondria upon acute paraquat administration.The data of Fig. 2a-KCN-sensitive respiration (in the article by Czerniczyniec et al. 2015) correspond to the consumption of oxygen only by the striatum mitochondria, and do not include that which takes place in the process of paraquat redox cycling. The authors consider the decreases shown in this Fig. 2a, for paraquat state 4 as well as for paraquat state 3 as strong evidence of a dysfunction of the bioenergetics of the mitochondria isolated from the striatum of the brain upon acute paraquat administration. But these data do not reflect a mitochondrial dysfunction. The RC is the fundamental parameter that indicates the energetic coupling of the mitochondria, and the researchers Czerniczyniec et al. consider that to be the case, writing (see page 400, first paragraph): BThe respiratory control ratio (the most sensitive indicator of mitochondrial oxidative phosphorylation coupling).^Nevertheless, these researchers do not report the RC calculated on the basis of their data presented in Fig. 2a (KCN-sensitive respiration). On calculating the RC (RC = state 3/state 4) on the basis of these data, (Fig. 2a of the article by Czerniczyniec et al. (2015)), an average value for the control RC of 5.9 and for the paraquat RC of 11.0 is obtained. These values show something surprising: the paraquat striatum brain mitochondria exhibit a greater degree of oxidative phosphorylation coupling, indicating that they are no subject to a dysfunction of their energetic state upon acute paraquat administration. In the same way, it is curious to observe (in the Bapparent^parameters of the mitochondrial respiration shown in Table 1 of the article by Czerniczyniec et al. (2015)) for the RC of the cerebral cortex mitochondria (control RC = 4.6 ± 0.2 and paraquat RC = 5....