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The ability to induce a hypothermia resembling that of natural torpor would be greatly beneficial in medical and non-medical fields. At present, two procedures based on central nervous pharmacological manipulation have been shown to be effective in bringing core body temperature well below 30°C in the rat, a non-hibernator: the first, based on the inhibition of a key relay in the central thermoregulatory pathway, the other, based on the activation of central adenosine A1 receptors. Although the role of mitochondria in the activation and maintenance of torpor has been extensively studied, no data are available for centrally induced hypothermia in non-hibernators. Thus, in the present work the respiration rate of mitochondria in the liver and in the kidney of rats following the aforementioned hypothermia-inducing treatments was studied. Moreover, to have an internal control, the same parameters were assessed in a well-consolidated model, i.e., mice during fasting-induced torpor. Our results show that state 3 respiration rate, which significantly decreased in the liver of mice, was unchanged in rats. An increase of state 4 respiration rate was observed in both species, although it was not statistically significant in rats under central adenosine stimulation. Also, a significant decrease of the respiratory control ratio was detected in both species. Finally, no effects were detected in kidney mitochondria in both species. Overall, in these hypothermic conditions liver mitochondria of rats remained active and apparently ready to be re-activated to produce energy and warm up the cells. These findings can be interpreted as encouraging in view of the finalization of a translational approach to humans.

We recently showed that the long-term in vivo administration of green tea catechin extract (GTE) resulted in hyperdynamic cardiomyocyte contractility. The present study investigates the mechanisms underlying GTE action in comparison to its major component, epigallocatechin-3-gallate (EGCG), given at the equivalent amount that would be in the entirety of GTE. Twenty-six male Wistar rats were given 40 mL/day of a tap water solution with either standardized GTE or pure EGCG for 4 weeks. Cardiomyocytes were then isolated for the study. Cellular bioenergetics was found to be significantly improved in both GTE- and EGCG-fed rats compared to that in controls as shown by measuring the maximal mitochondrial respiration rate and the cellular ATP level. Notably, the improvement of mitochondrial function was associated with increased levels of oxidative phosphorylation complexes, whereas the cellular mitochondrial mass was unchanged. However, only the GTE supplement improved cardiomyocyte mechanics and intracellular calcium dynamics, by lowering the expression of total phospholamban (PLB), which led to an increase of both the phosphorylated-PLB/PLB and the sarco-endoplasmic reticulum calcium ATPase/PLB ratios. Our findings suggest that GTE might be a valuable adjuvant tool for counteracting the occurrence and/or the progression of cardiomyopathies in which mitochondrial dysfunction and alteration of intracellular calcium dynamics constitute early pathogenic factors.

Dysfunctions caused by genetic defects in the mitochondrial DNA (mtDNA) of humans are called mitochondrial diseases; however, mtDNA mutations are also associated with aging and age-related diseases. Here, we present an original cellular model that allows gathering information on molecules that might contrast or prevent mitochondrial dysfunctions and their related diseases. This model allowed us to show that resveratrol (RSV), a phytochemical present in food, exerts protective effects at low concentrations on resting human fibroblasts carrying dysfunctional respiratory chain Complex I. Cells were maintained both in resting condition, to mimic the high energy demanding post-mitotic tissues (serum absence and gramicidin presence), and under glucose deficiency to push the synthesis of ATP via oxidative phosphorylation. Pre-incubation with RSV prolonged the viability of the fibroblasts exposed to rotenone, a well-known specific inhibitor of the respiratory chain Complex I, and decreased mitochondrial fragmentation. It significantly prevented the oxidative phosphorylation impairment indirectly caused by the rotenone-mediated Complex I inhibition, allowing for an almost complete preservation of the cellular ATP level. Indeed, RSV limited the rotenone-induced reactive oxygen species increase, allowing for the maintenance of a functional mitochondrial membrane potential. These findings indicate the potential usage of resveratrol to prevent or possibly treat many disorders, in which the bioenergetic defects and oxidative stress are the primary (mitochondrial encephalomyopathy), or the secondary (age-related diseases) causes of the pathology; and to also assist cell senescence during aging.