A Walk in the Memory, from the First Functional Approach up to Its Regulatory Role of Mitochondrial Bioenergetic Flow in Health and Disease: Focus on the Adenine Nucleotide Translocator

We cannot currently provide any molecular mechanism underlying how CFTR dysfunction affects so many parameters of mitochondrial function, and in particular on ANT activity, nor how corrector-induced increased expression of cell surface CFTR is able to repair these mitochondrial dysfunctions. However, the data per se, beyond strongly suggesting that the restorative action provided by the correctors in CF cells is linked to the rescue of chloride channel activity, corroborate the validity of the method by which ANT activity was measured since the small corrector molecules have no effect per se on mitochondrial function in control-CFTR cells.

In this review we discussed the wide relevance of the ATP detecting system performed to measure the ANT-mediated ADP/ATP exchange by highlighting the essential aspects of its versatile applicability in pathophysiology. We undertook this study, in which literature data alternates with our own stories concerning our personal steps taken in the scientific world, after “taking a walk” through Google Scholar and realizing that all the research concerning ADP/ATP exchange as well as the synthesis of ATP via OXPHOS, measured under conditions as close as possible to the real ones, i.e., by using the ATP D.S., had received less visibility, i.e., fewer citations, than it deserves given the importance of the topic.

This was the reason that prompted us to group all the studies reported above in an attempt to create a sort of common thread that goes from the very first experimental attempt to continuously measure the OXPHOS process of mitochondrial ATP synthesis, through all the uses that have been made of this method—remaining still “new” for those who do not yet know it—up to its current application in a more complex study that saw cell systems and/or tissues carrying genetic and/or induced diseases as a playing field through the use of specific effectors.

We hope that it will be of help to researchers who want to adopt it in the future.