The role of mitochondrial calcium uniporter in neuroprotection in traumatic brain injury

Abstract

The alteration in cellular Ca(2+) homeostasis is one of the key mechanisms contributing to secondary neuronal damage and altered physiology during the process of traumatic brain injury (TBI). However, there is considerable uncertainty about the efficacy of calcium channel blockers in randomized, controlled, clinical trials. In the physiological condition, cellular Ca(2+) homeostasis occurs through repetitive bursts of rising intracellular Ca(2+) that, sometimes are referred to as Ca(2+) oscillations. Mitochondria are intimately involved in the spatiotemporal tuning of cellular Ca(2+) signaling mainly through mitochondrial Ca(2+) uniporter (MCU). Excessive Ca(2+) uptake by the mitochondria through MCU is a key event in mitochondrial dysfunction and cell death in TBI. Selective inhibition of MCU has showed a promising cardioprotection and neuroprotection effect in many preclinical studies. Based on these preclinical results, the selective inhibition of MCU may be a new strategy for neuroprotection in TBI patients.