Thanks for your prompt reply and thank you for being willing to discuss these topics.You see, since our little-known laboratory has discovered the existence of extramitochondria structures according to rigorous laboratory measurements and we have shown that these structures are the real producers of large quantities of ATP serving the cell, I had almost no supporter and many detractors. Worse, with me it just does not compare. So thank you to speak to us and I hope that this comparison continues.

Evolution is a fluid matter because in laboratory experiments are impossible to do, as my friend  Telmo Pievani (I think you know him) says. In fact, we should go back millions of years for realize the experiments...

According then to this is a certain fact, although inconvenient, I understand ... but mitochondria do not produce ATP for the cell. The ATP is produced by extramitochondrial structures. This is not a matter of debate, but an experimental measure accessible to anyone, even your very important  biochemical laboratories in Dusseldorf.

There is a project of mine on ResearchGATE that I invite you to take note of it:

Comparison of ATP produced by the mitochondria and myelin

Link:  https://www.researchgate.net/project/Comparison-of-ATP-produced-by-the-mitochondria-and-myelin

However, the central question that I think you may not be refuted as follows:

If the ancestral eukaryotes have engulfed prokaryotes for food (suicide hypothesis of Martin, or wrong?) why these prokaryotes would have to produce for those who wanted to eat it the ATP which is the most precious produce a cell?

Anyway I do not think that has been disproved my observation that the vision would be a canonical parasitism and not a symbiosis. I think my speculation instead twisted the possible adaptations in a form of symbiosis.

However, I have no evolutionary skills. I am a chemist in love with the chemistry of living organisms and reason in terms particularly stoichiometric and quantitative. I think on the mitochondria there is a lot to know and believe that the "foundations" on the mitochondria of our textbook are deeply reviewed. We want to talk about it?

Thanks if you extend these considerations to your authoritative colleagues.

Thank you very much indeed!

Yours sincerely,

      Alessandro Morelli

I still thought about your skepticism on my proposals and return to the concept that an account have the data to another are the ideas and speculations. To formulate my proposals rather non-conformist, they set off from having found that the mitochondria do not produce the bulk of ATP necessary for a cell eucariota.Esistono our measures very precise laboratory, which confirm literature data, according to which it appears mitochondria are a niche where you can assemble the complicated machinery of oxidative phosphorylation, machinery that can not be operational in the mitochondria themselves because it would produce too many free radicals that damage the DNA of the mitochondria itself. Logic dictates that such machinery is exported elsewhere away from mitochondrial DNA and nuclear DNA and mitochondria have a series of fusion proteins that are used precisely for this purpose. The ER accepts the machinery and can operate fully for aerobic ATP synthesis being fed by reducing equivalents produced by the Krebs cycle very active in the cytosol. We have two papers on the Krebs cycle in the cytosol published in Biochimie 1,2

So mine is not an "idea" which originated from theoretical elaboration, but rests on these laboratory findings. We want to confront on these? I propose a dispute, and disputes are the culture broth of Science. On the other hand the proposed dispute already in Nature in 2011 in Martin & Lane but and they refuted my proposals with arguments that now appear outdated. We want to update the comparison?

     1.   Ravera, S. et al. Tricarboxylic acid cycle-sustained oxidative phosphorylation in isolated myelin vesicles. Biochimie 95, 1991–1998 (2013).

2.        Panfoli, I. et al. Extramitochondrial tricarboxylic acid cycle in retinal rod outer segments. Biochimie 93, 1565–75 (2011).

I still go back to talk about these topics because I believe deeply in the comparison between scientists for the advancement of science. I quote the encouragement of Sir John Walker, who wrote me:

Dear Professor Morelli, You have made your rather radical proposal based on your experiments, and you have reported your findings in the literature. In general, the scientific community is rather conservative, tends to resist new ideas, and asks for independent verification, which seems to be lacking in your case. However, if they are correct, eventually their truth will be realised. As one of my mentors, Max Perutz,  famously remarked: “In Science, truth wins”. 

With my best wishes

John Walker

Now I know that this amazing figure (That is, that the bulk of the ATP of a eukaryotic cell is produced outside of the mitochondria) is confirmed only by our published work , and other laboratories should play our data as would an established scientific practice, but I do know that as many as 3 authoritative laboratories have begun to play our experiments and stopped when ... they saw that things were as we said.

I believe that making experimental clarity on this would exceed all sorts of speculations also absolutely plausible. I want to add that the heart of the matter is related to the forces that drive the universal FoF1ATP ATP Synthase. The idea widely accepted by all is that such force is the membrane potential / protomotive power, but in 2013, I published a Hypothesis  that would make such an independent synthesis of this potential 1, however, also provided by research carried out in Russia 2 for e direct coupling, which rouled out le link to membrane potential/protomotive power .

Then I would like to know if you have given the discovery made recently  3 about a eukaryote that has no mitochondria.

Given all of this I believe that the effective role of mitochondria are many things to be reviewed, because I think we can all agree that the idea that they are the "power house" of the cell is too simplistic.

1.           Morelli, A. M., Ravera, S., Calzia, D. & Panfoli, I. Hypothesis of lipid-phase-continuity proton transfer for aerobic ATP synthesis. J Cereb Blood Flow Metab 33, 1838–1842 (2013).

2.           Eremeev, S. A. & Yaguzhinsky, L. S. On local coupling of electron transport and ATP-synthesis system in mitochondria. Theory and experiment. Biochem. 80, 576–581 (2015).

3.           Karnkowska, A. et al. A Eukaryote without a Mitochondrial Organelle. Curr. Biol. 26, 1274–1284 (2016).