Your measurements are important to accept the evidence that mitochondria are not the only producers of ATP. Rather! There is evidence to assign the role of mitochondria mounting site of the mitochondrial machinery for export to other cellular district by fusion heterologous where ATP synthesis can occur without restrain. This does not detract from the importance of mitochondria, indeed, it increased. The ATP thus is produced locally where it is needed. I send a ns. latest publication on the evolution of mitochondria and our years ago sull'ATP synthasi of plasma membranes. I can assure you that ATP synthase synthesizes ATP not due to the membrane potential, but there is a direct coupling proton and protons never leave the membrana.Infatti how can accukmularsi if all membranes are permeable to protons? A Polish colleague has published one article that definitively eliminates the idea that protons accumulate from one side of the membrane (I enclose). The Mitchel theory requires a deep reorganization. I'd like to keep in touch.
Dear Alessandro.
Thank you for your interest and your questions about my article.
The proposed function of Oxidative phosphorylation systems in plasma membrane (exOXPHOS) thought to be ATP by forming proton gradient by NADH which is an electron donor. However, our results show that exOXPHOS did not have NADH-dependent sarcolemmal respiration activity. In your opinion, ATP may be generated by direct coupling, not by membrane potential.
According to my recent studies using immuno-gold electron microscopy, the mitochondrial respiratory protein was present in the contact site of the mitochondrial and plasma membrane (Unpublished data). However, I am still thinking that the partial of membrane potential is formed by exOXPHOS. According to my ongoing paper, I have observed the production of extracellular superoxide by a proton gradient of plasma membrane oxidative phosphorylation system. These results indicate that extracellular superoxide can be formed through at least the proton gradient formed in the plasma membrane, because the inhibition of other extracellular ROS - producing proteins is not affected by these results.
Thus, although plasma membrane OXPHOS system does not affect the ATP production by the proton gradient, it may have some influence on extracellular ROS production.
For any suggestions and in information please ask me.
Best regards.
Hyun Lee
In our laboratory we have preliminary data which look very interesting: both myelin that discs of the photoreceptors are capable of accumulating energy, properties absolutely not possessed by the mitochondria. For the myelin open up exciting prospects for) a possible myelin energy role in managing the memory. ii) myelin can play an energetic role in sleep. We confirm again that the mitochondria appear to be the station of mounting of OXPHOS machinery (it’s requires a single seat for subcellular build OXPHOS, given that some proteins are encoded by mitochondrial DNA and other nuclear DNA). Such machinery can be exported to other locations, the endoplasmic reticulum in the first place, thanks to the various fusion proteins possessed by mitochondria (OPA1, mitofusin 1, Drp1, and so on)
Bioenergetics requires radical changes
The research activity carried out by the Morelli-Panfoli-Ravera-Calzia group (Genoa University, Italy) highlights that many basic concepts of biochemistry require a radical update. Since scientists can communicate with each other only if they refer to the same paradigms, this must be premised in any scientific debate and dissemination activity. The proposed paradigm changes are set out below:
1) The history of mitochondria suffers from too many assumptions that have never been verified. Since mitochondria contain a significant number of molecules that carry out Oxidative Phosphorylation (OXPHOS) with the coupled recharge of ATP (i.e. the transfer to ADP of a residue of orthophosphoric acid with the formation of ATP) in the 1950s everyone believed that the mitochondria held the exclusive supply of ATP to the cell. However, since laboratory measurements denied this assumption (isolated mitochondria produce about 10 nanomoles of ATP / min / mg. Of protein, that is, very little), the P / O ratio was introduced around the 1960s to evaluate the efficiency of mitochondria. A methodological error that still weighs on the study of mitochondria. In fact, the P / O ratio can also be suitable to indicate ATP production capacity but, being the ratio between two flows, the ATP produced and the atomic oxygen consumed, the P / O ratio is a dimensionless quantity completely independent of the real fluxes of metabolites. The P / O ratio can also fall within the canonical values, but the ATP recharge can also be insignificant.
2) The group of biochemists at the University of Genoa experimentally confirmed what was stated in point 1) but also verified that the mitochondria, while not producing ATP for the cell - therefore would be refuted a pillar of bioenergetics - however, they perform an even more important function: the microvesiculation of the internal membrane with the production of microvesicles-exosomes chargo that are sent to the intracellular and even extracellular membranous districts to make them capable, the latter, of producing ATP without the drastic limitations linked to the double membrane that surrounds the mitochondrion. Recently, in confirmation of this, Pasquale D'Acunzo's group identified extracellular exosomes that contain mitochondrial devices which he himself called "mitovesicles" (D’Acunzo et al., 2021).
3) Various intracellular structures certainly receive the OXPHOS molecular machinery from the mitochondria i) all the discs of the outer segments of the rods of the retina, which have a significant capacity to recharge ATP (about 400 nanomoles / min / mg of proteins) (Panfoli et al., 2009) and supply - the discs - the energy for the phototransduction process which, as is known, is a process with a high energy expenditure; ii) we have measured the recharges the ATP (about 80 nanomoles / min / mg of protein) (Ravera et al., 2021) by myelin sheath which send ATP to the axon to support the advancement of the nerve signal. We can say in metaphorical language that myelin is like a gigantic mitochondrion that presides over the high energy processed by the brain.
It is understood that from all this more than one current paradigm of biology and neurobiology should be replaced by others as proposed in the recent article (Morelli, 2022).
References
D’Acunzo, P., Pérez-González, R., Kim, Y., Hargash, T., Miller, C., Alldred, M.J., Erdjument-Bromage, H., Penikalapati, S.C., Pawlik, M., Saito, Mitsuo, Saito, Mariko, Ginsberg, S.D., Neubert, T.A., Goulbourne, C.N., Levy, E., 2021. Mitovesicles are a novel population of extracellular vesicles of mitochondrial origin altered in Down syndrome. Sci Adv 7. https://doi.org/10.1126/sciadv.abe5085
Morelli, A.M., 2022. A new way of understanding bioenergetics. Res Featur. https://doi.org/10.26904/RF-142-2921655847
Panfoli, I., Calzia, D., Bianchini, P., Ravera, S., Diaspro, A., Candiano, G., Bachi, A., Monticone, M., Aluigi, M.G., Barabino, S., Calabria, G., Rolando, M., Tacchetti, C., Morelli, A., Pepe, I.M., 2009. Evidence for aerobic metabolism in retinal rod outer segment disks. Int J Biochem Cell Biol 41, 2555–65. https://doi.org/10.1016/j.biocel.2009.08.013
Ravera, S., Bartolucci, M., Calzia, D., Morelli, A.M., Panfoli, I., 2021. Efficient extra-mitochondrial aerobic ATP synthesis in neuronal membrane systems. J Neurosci Res. https://doi.org/10.1002/jnr.24865
Notes written by Alessandro Maria Morelli ([email protected])
Genoa (Italy), 15 September 2022
The question of who actually produces ATP for the cell still awaits an answer today and continues to be a conundrum of biology. In the short notes "Bioenergetics requires radical changes" (attached) I have summarized 3 fundamental points to address the problem. Until it is resolved, there is little hope of identifying the causes that trigger diseases such as Alzheimer's and Parkinson's.
I trust that the document will start a stimulating discussion.