Bergamot derivative compounds affect on F1FO-ATPase and the mitochondrial permeability transition

The albedo and pulp of bergamot are rich sources of fibers and polyphenols [1]. Bergamot fiber (BF) confers a beneficial effect on the gut microbiota and can be considered prebiotics. The bergamot polyphenolic fraction (BPF) is used in the form of nutraceuticals with countless beneficial properties such as anticancer, antiviral and anti- inflammatory, antioxidant, cardioprotective, and lipid-lowering [2]. The F1FO-ATPase is considered the leading candidate responsible for the mitochondrial permeability transition pore (mPTP) formation when the natural cofactor Mg2+ is replaced with Ca2+ [3]. We tested BF, BPF or a mixture of both on swine heart mitochondria to evaluate the effect on mitochondrial bioenergetics. The F1FO-ATPase activity, dependent on the natural cofactor Mg2+ increased by 15%, whereas the enzyme activity in the presence of Ca2+ was inhibited by 10% with 100 μg/mL BPF. Conversely, BF did not affect the Mg2+- or Ca2+-activated F1FO-ATPase. mPTP formation, measured as calcium retention capacity, was inhibited with BPF or BF. The correlation index (CI) will be calculated to evaluate the pharmacological interaction between BPF and BF to define synergism (CI < 1), antagonism (CI > 1) or additive (CI = 1) effect.