Mitochondria Bioenergetic Functions and Cell Metabolism Are Modulated by the Bergamot Polyphenolic Fraction

Abstract

The bergamot polyphenolic fraction (BPF) was evaluated in the F1FO-ATPase activity of swine heart mitochondria. In the presence of a concentration higher than 50 µg/mL BPF, the ATPase activity of F1FO-ATPase, dependent on the natural cofactor Mg2+, increased by 15%, whereas the enzyme activity in the presence of Ca2+ was inhibited by 10%. By considering this opposite BPF effect, the F1FO-ATPase activity involved in providing ATP synthesis in oxidative phosphorylation and triggering mitochondrial permeability transition pore (mPTP) formation has been evaluated. The BPF improved the catalytic coupling of oxidative phosphorylation in the presence of a substrate at the first phosphorylation site, boosting the respiratory control ratios (state three/state four) by 25% and 85% with 50 µg/mL and 100 µg/mL BPF, respectively. Conversely, the substrate at the second phosphorylation site led to the improvement of the state three/state four ratios by 15% only with 100 µg/mL BPF. Moreover, the BPF carried out its beneficial effect on the mPTP phenomenon by desensitizing the pore opening. The acute effect of the BPF on the metabolism of porcine aortica endothelial cells (pAECs) showed an ATP rate index greater than one, which points out a prevailing mitochondrial oxidative metabolism with respect to the glycolytic pathway, and this ratio rose by about three times with 100 µg/mL BPF. Consistently, the mitochondrial ATP turnover, in addition to the basal and maximal respiration, were higher in the presence of the BPF than in the controls, and the MTT test revealed an increase in cell viability with a BPF concentration above 200 µg/mL. Therefore, the molecule mixture of the BPF aims to ensure good performance of the mitochondrial bioenergetic parameters.

The Impairment of Cell Metabolism by Cardiovascular Toxicity of Doxorubicin Is Reversed by Bergamot Polyphenolic Fraction Treatment in Endothelial Cells

“…It has been ascertained that features of bergamot polyphenolic fraction (BPF) boost the bioenergetic parameters of mitochondria, improve cellular oxidative metabolism and block molecular events in mitochondria that trigger different forms of regulated cell death [ 1 ].…”

“…The soil and the microclimate of this geographical area are decisive for the organoleptic characteristics of bergamot, in particular for its high concentration of polyphenols [ 18 , 19 ]. As regards antioxidant and anti-inflammatory action and the reduction of hyperlipidemia and hyperglycemia, these are attributable to BPF, which represents the polyphenol-rich fraction obtained from the juice and albedo of bergamot [ 1 ]. In recent years, researchers have been looking for treatments that can reduce the cardiotoxicity of DOX [ 20 ].…”

“…The mPTP phenomenon is triggered by Ca 2+ -activated F 1 F O -ATPase [ 23 ]. Furthermore, in the presence of BPF, we observed a reduction in the opening of mPTP [ 1 ]. The study also demonstrated the effect of BPF on cellular metabolism and demonstrated an effect on ATP production in porcine aortic endothelial cells (pAECs) [ 1 ].…”

“…Furthermore, in the presence of BPF, we observed a reduction in the opening of mPTP [ 1 ]. The study also demonstrated the effect of BPF on cellular metabolism and demonstrated an effect on ATP production in porcine aortic endothelial cells (pAECs) [ 1 ]. Notably, BPF did not affect total intracellular ATP levels, but increased ATP production was observed through oxidative metabolism rather than through glycolysis.…”

“…Cell viability also increased in the presence of BPF. Therefore, that study made it possible to obtain an innovative result relating to the positive effect of BPF on mitochondrial bioenergetics and oxidative metabolism [ 1 ].…”