@pittybitty said in What is Metabolic Uncoupling?:
why is metabolic uncoupling such a sought after property in the peat-sphere?
From what I've understood so far:
Short version:
Mitochondrial uncoupling makes reference to the use of ATP, not for energy production but for “respiration” or other biological processes (thermogenesis and defense against oxidative damage: ROS).
According to RP
When mitochondria are “uncoupled,” they produce more carbon dioxide than normal, and the mitochondria produce fewer free radicals.
Source: Protective CO2 and aging.
https://raypeat2.com/articles/articles/protective-co2-aging.shtml
Full explanation (to be confirmed):
Uncoupling mitochondria
What is the role of uncouplers in mitochondrial function and energy production?
The uncoupling proteins (UCP) are transporters, present in the mitochondrial inner membrane, that mediate a regulated discharge of the proton gradient that is generated by the respiratory chain, to serve functions such as thermogenesis, maintenance of the redox balance, or reduction in the production of reactive oxygen ... (PMC2924931)
Explained differently: Mitochondrial uncoupling makes reference to the use of ATP, not only for energy production but for “respiration” or other biological processes (thermogenesis and defense against oxidative damage: ROS).
Source: ScienceDirect.com (PMC151194)
When we partially bypass the natural process of producing energy (through the uncoupling process), we limit the production of ROS. The attenuation of ROS by partial uncoupling while maintaining sufficient ATP production would be a potential mechanism for delaying cellular senescence (Papa and Skulachev, 1997; Brand, 2000).
According to RP
When mitochondria are “uncoupled,” they produce more carbon dioxide than normal, and the mitochondria produce fewer free radicals.
Note (LucH): CO2 is very important when trying to lower stress induced by metabolism or other "intruders".
Source: Protective CO2 and aging.
https://raypeat2.com/articles/articles/protective-co2-aging.shtml
Natural uncouplers
FFAs form one of the major class of endogenous mitochondrial uncouplers. They can act through various mechanisms. First, they stimulate directly mitochondrial respiration, as seen in intact isolated brown adipocytes or mitochondria isolated from these cells [28,29].
Capsaicins and their derivatives are red-pepper components and are long known for their capacity to induce the upregulation of uncoupling proteins, even in vivo [62]. The molecular mechanisms are still unclear but could involve sympathetic stimulation [63,64].
T3 Thyroid hormone. Among the natural endogenous molecules with uncoupling properties, one can also cite the thyroid hormone T3. T3 regulates mitochondrial uncoupling by different mechanisms: (1) by sympathetic stimulation [61], (2) by increasing acylcarnitine production [61], thereby activating mitochondrial respiration/uncoupling, and (3) by directly stimulating the transcription of the Ucp1 gene [37].
Cellular response to uncoupling
It can be easily understood that the activation or induction of mitochondrial uncoupling will lead to the activation of cellular mechanisms/responses in order to cope with induced stress and/or to regulate this process. For instance, a severe mitochondrial uncoupling can lead to rapid cellular ATP depletion and, if the stress persists, to the triggering of other cellular mechanisms, such as cell death.
