Are Tetracyclines OXPHOS Uncouplers?

[methylenewhite]

Came across this paper mentioning subgroups of uncouplers:
THE UNCOUPLING OF OXIDATIVE PHOSPHORYLATION AS A MECHANISM OF DRUG ACTION

Study of these latter substances, the uncoupling agents, reveals further subgrouping: 1) those agents which stimulate oxygen consumption and are insensitive to magnesium ion changes (e.g., dinitrophenol) and 2) agents which do not stimulate oxygen consumption while depressing phosphorylation and whose action is reversed by magnesium ions (e.g., the tetracyclines). The significance of this difference remains to be explained.

Are tetracyclines indeed OXPHOS uncouplers?

Does anybody able to explain this magnesium ions sensitivity and how to use it?

 

[yerrag]

agents which do not stimulate oxygen consumption while depressing phosphorylation and whose action is reversed by magnesium ions (e.g., the tetracyclines).

I don't know if this is relevant, but after taking doxycyline for a while, I noticed that my temperature has gone down by at least 0.5 C. I'm not sure if this is the direct result of prolonged use of doxycycline (as it could be that less bacteria has lowered the innate immune system response, thus mininimizing the temperature increasing action of immunity), but if it is, would increased intake of magnesium be able to increase phophorylation and thus increase my body temperature?

 

[methylenewhite]

I don't know if this is relevant, but after taking doxycyline for a while, I noticed that my temperature has gone down by at least 0.5 C. I'm not sure if this is the direct result of prolonged use of doxycycline (as it could be that less bacteria has lowered the innate immune system response, thus mininimizing the temperature increasing action of immunity), but if it is, would increased intake of magnesium be able to increase phophorylation and thus increase my body temperature?

No idea. In my original post I asked for help to interpretate it.

 

[SOMO]

Apparently Magnesium also stops the Uncoupling induced by T4.

https://www.jbc.org/content/228/2/573.full.pdf

It is obvious that the effects of magnesium deficiency and thyroxine excess produce a similar uncoupling of oxidative phosphorylation. Both effects are reversible by magnesium administration.

It has something to do with the requirement of Mg2+ to produce ATP.

The effect of magnesium on oxidative phosphorylation and mitochondrial adenosine triphosphatase - ScienceDirect

3. It is concluded that the Mg2+-stimulated ATP-ase and the DNP-stimulated ATP-ase differ in the nature of their hydrolytic reaction, but that both contain the same phosphorylation reaction, which is moreover the same as that in oxidative phosphorylation, but in the opposite direction.

So I think low Magnesium = less ATP being produced = energy being diverted towards Heat Production. (i.e. "Uncoupling.)
Adequate Magnesium = More ATP = less Uncoupling.

So if you provide more Magnesium, you will reduce uncoupling by increasing ATP generation.

I wonder if this means ANYTHING that interferes with ATP production will increase heat-production/uncoupling.