The role of mitochondrial uncoupling in the regulation of mitostasis after traumatic brain injury

Mitostasis, the maintenance of healthy mitochondria, plays a critical role in brain health. The brain’s high energy demands and reliance on mitochondria for energy production make mitostasis vital for neuronal function. Mild mitochondrial uncoupling, which dissociates ATP production from oxygen consumption, offers a promising avenue for TBI treatment. Accumulating evidence, from endogenous and exogenous mitochondrial uncoupling, suggests that mitostasis is closely regulating by mitochondrial uncoupling and cellular injury environments may be more sensitive to uncoupling. Mitochondrial uncoupling can mitigate calcium overload, reduce oxidative stress, and induce mitochondrial proteostasis and mitophagy, a process that eliminates damaged mitochondria. The interplay between mitochondrial uncoupling and mitostasis is ripe for further investigation in the context of TBI.

• 1
  Deficits in mitochondrial function and metabolism are considered driving forces in progressive energy crisis developed after TBI.
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  Mild mitochondrial uncoupling lowers mitochondrial Ca2+ overload, which prevents the opening of the mPTP. Given the driving potential for Ca2+ uptake into mitochondrial, even a small depolarization of the mitochondrial membrane potential can reduce driving force of Ca2+ uptake several fold.
• 3
  Mild mitochondrial uncoupling is a powerful and translational approach as it modulates mitochondrial biophysics, rather than targeting a specific protein or cytokine.