The endoplasmic reticulum (ER) and mitochondria have both been shown to be critical in cellular homeostasis. The functions of the ER and mitochondria are independent but interrelated. These two organelles could form physical interactions, known as MAMs, to regulate physiological functions between ER and mitochondria to maintain Ca2+, lipid, and metabolite exchange. Several proteins are located in MAMs, including RNA-dependent protein kinase (PKR)-like ER kinase, inositol 1,4,5-trisphosphate receptors, phosphofurin acidic cluster sorting protein-2 and sigma-1 receptor to ensure regulation. Recent studies indicated that MAMs participate in inflammation and apoptosis in various conditions. All of these functions are crucial in determining cell fate following traumatic brain injury (TBI). We hypothesized that MAMs may associate with TBI and could contribute to mitochondrial dysfunction, ER stress, autophagy dysregulation, dysregulation of Ca2+ homeostasis, and oxidative stress. In this review, we summarize the latest understanding of MAM formation and their potential regulatory role in TBI pathophysiology.
Keywords: Apoptosis; Inflammation; Mitochondria-associated ER membranes; Traumatic brain injury.