ETC uncoupling

[basophilic]

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According to KA passage, brown fat contains uncoupler proteins in inner mitochondrial membrane that allow protons to flow down w/o making ATP; the flowing down concentration gradient releases heat needed for infants. Then a question stated the following:

Increasing the permeability of the inner mitochondrial membrane would have what effect on brown fat cells?

A. More heat production, More ATP production
B. Less heat production, Less ATP production
C. More heat production, ATP production unaffected
D. Less heat production, ATP production unaffected

Answer was B. While I agree that less ATP will be produced, why would heat production decrease by "increasing permeability of inner membrane"? Some type of uncoupling agent would have been necessary to increase permeability, and the downflow of protons will be exothermic REGARDLESS of what uncoupling agent you use, no?

 

[MrRed]

The only reason I would pick B readily is because ATP production HAS to decrease; and it is the only option with this effect stated.

I tend to agree with you in the event that UCP is not already fully active.
If you increase the permeability of the IMM then protons will be increasingly able to flow down their concentration gradient into the matrix, thus dissipating the electrochemical gradient at an increased rate. To compensate for this, the ETC will have to work even harder (as even less of the energy harnessed from the electron transport is being used to actually make ATP). Thus, heat production should increase and ATP synthesis should decrease.

However; in the event that UCP is considered fully active; which I assume it is as they specifically state "brown fat mitochondria" in the passage, I believe it comes down to what follows:
The increase in permeability (an additive to the excess permeability already introduced by significant quantities of UCP) is summed to such an extent that the actual electrochemical gradient created from proton transport is prevented from reaching near its typical value (which I believe is about 21kJ/molH+ give or take) which would result in less overall driving force, and less heat production overall. In this case the gradient is not as large and thus it is less exothermic for the protons to diffuse from the IMspace into the matrix across the IMM.

I suppose this would make sense -- as the brown fat mitochondria can already be assumed to have a significant increase in permeability due to the presence of UCP's and any extra increase in permeability would simply prevent an effective gradient from forming at all.

At some point in permeability of the IMM; the proton gradient will not be able to actually form; as protons will have diffused rapidly to nearly equalize the concentration. In the case of uncouplers on their own, at a low dose mind you, (consider DNP, at a low dose) this is unlikely to happen. The 3 pump complexes of the ETC can actually maintain the electrochemical gradient and continue to allow for ATP synthesis; however they must work harder to do so.

However, lets just say you're a bodybuilder trying to cut up (lose fat) for the show, and you're not aware that DNP actually accumulates in your system -- to a substantial extent -- and that dosing only 200mg/day (or even less in some cases) should be adequate for your fat-loss needs in ~2 weeks; albeit making you one miserable son-of-a-gun.
So, instead you decide to take; oh I don't know; 1gram a day of DNP. Well, after a few days what happens? You die.
Why? Because literally you have completely diffused the entire proton gradient; it can't even form because it is essentially like the membrane isn't even there anymore -- there's just a giant hole. So every time the ETC complexes pump a proton, it's just like moving it to the same space it started in.

So that would be my best go at an explanation; and is really the only one I can think of that makes sense. If there is significantly less driving force, there is less heat.

Sorry for the long response to the simple question -- I always get way too into this stuff.

 

[basophilic]

I see, but if the actual proton gradient is decreased due to worse segregation, wouldn't the body try to compensate with increased burning up of fuel and increased O2 consumption; heck, the cells care most about the ATP their mitochondria are generating, so I might even expect the cell to create a larger H+ gradient - some can be used for dissipation (which would probably have faster rate than ATP synthesis) and leave enough for ATP synthase.
And I agree, the latter half of the answer choice was the only reason I had to pick B.