What is mitochondrial uncoupling? by Steven Fowkes

Answer by Steven Fowkes:

Uncoupling is a loss of output efficiency for any given input to a process. Mitochondrial uncoupling is the loss of ATP production from the input of protons into the inter-membrane space. This can be protein driven as part of a natural feedback loop for the regulation of energy and temperature, and it can be chemical / toxin driven.

I think 2,4-dinitrophenol is the classic uncoupling toxin for much of the research in this area. You also mention aspirin, which also has an uncoupling effect.

If you measure energy by ATP formation, uncoupling can decrease energy. But not necessarily always. Thermogenic agents like caffeine and ephedra can increase both ATP and fuel consumption to compensate for uncoupling inefficiencies.

If you measure energy by fuel consumption (a caloric perspective), uncoupling can increase energy production. This is most conspicuous in brown-fat tissues exposed to cold, but it might also play a strong role in the generation of fever responses to sepsis.

Thanks for the question.

What is mitochondrial uncoupling?