The Role Played by Mitochondria in FcεRI-Dependent Mast Cell Activation

Abstract

Mast cells play a key role in the regulation of innate and adaptive immunity and are involved in pathogenesis of many inflammatory and allergic diseases. The most studied mechanism of mast cell activation is mediated by the interaction of antigens with immunoglobulin E (IgE) and a subsequent binding with the high-affinity receptor Fc epsilon RI (FcεRI). Increasing evidences indicated that mitochondria are actively involved in the FcεRI-dependent activation of this type of cells. Here, we discuss changes in energy metabolism and mitochondrial dynamics during IgE-antigen stimulation of mast cells. We reviewed the recent data with regards to the role played by mitochondrial membrane potential, mitochondrial calcium ions (Ca 2+) influx and reactive oxygen species (ROS) in mast cell FcεRI-dependent activation. Additionally, in the present review we have discussed the crucial role played by the pyruvate dehydrogenase (PDH) complex, transcription factors signal transducer and activator of transcription 3 (STAT3) and microphthalmia-associated transcription factor (MITF) in the development and function of mast cells. These two transcription factors besides their nuclear localization were also found to translocate in to the mitochondria and functions as direct modulators of mitochondrial activity. Studying the role played by mast cell mitochondria following their activation is essential for expanding our basic knowledge about mast cell physiological functions and would help to design mitochondria-targeted anti-allergic and anti-inflammatory drugs.

Mast Cells Mediate Inflammatory Injury and Aggravate Neurological Impairment in Experimental Subarachnoid Hemorrhage Through Microglial PAR-2 Pathway

“…On the one hand, the activated MCs could facilitate wound healing by recognizing antigens through pattern recognition receptors and the high-affinity immunoglobulin E receptor, resulting in the releasing of granules, which further mediates cell recruitment, fibrosis, angiogenesis, and extracellular matrix deposition ( Ozpinar et al, 2020 ). One the other hand, the cytoplasmic granules from MCs also contribute to multiple inflammatory and allergic pathogenesis diseases, including asthma, allergy, arthritis, interstitial cystitis, irritable bowel syndrome (IBD), ulcers, and prostatitis ( Chelombitko et al, 2020 ; Fu et al, 2020 ). Notably, accumulating studies implicate the role of MCs in CNS.…”

“…Mast cells (MCs), one of the granulocytes derived from the myeloid stem cell that widely distributed in tissues surrounding blood vessels, nerves, smooth muscle cells, and synovial membranes, are an important regulator participating in both innate immunity and adaptive immunity ( El Ansari et al, 2020 ). Upon activation, MCs could rapidly migrate to the site of injury and undergo degranulation by releasing the preformed mediators, including tryptase, chymase, histamine, heparin, serotonin, and prostaglandins into extracellular, which further recruit immune cells and amplify the inflammatory response ( Chelombitko et al, 2020 ). For years, MCs have been mainly studied due to their pathogenic role in allergic responses during the progression of urticaria and asthma ( Falduto et al, 2020 ).…”

Mitochondria, pattern recognition receptors and autophagy under physiological and pathological conditions, including viral infections

“…Mitochondria are cellular structures not only responsible for the production of energy necessary for cell metabolism by accumulation of ATP through oxidative phosphorylation, but also the place where genetic material is deposited -methylated mtDNA and unmethylated DNA called the CpG islands (Choi et al, 2020;Liu et al, 2016;West & Shadel, 2017). These organelles are also involved in anabolic and catabolic pathways, including regulation of cell signaling, apoptosis, ROS production, and calcium homeostasis (Chelombitko et al, 2020;Choi et al, 2020;Karmakar et al, 2019;Klein et al, 2020). The role of mitochondria is also related to the immune system, including infectious diseases (Choi et al, 2020;Ren et al, 2020).…”

“…It has been shown that during infection anabolism is changed into catabolism in immune cells, i.e. in T lymphocytes, including Treg, macrophages M1 and M2 (Chelombitko et al, 2020), neutrophils and mast cells (Chelombitko et al, 2020;Klein et al, 2020), thanks to which mitochondria are involved in molecular mechanisms coordinating energy processes (Chelombitko et al, 2020). Mitochondria in the T effector cells, M1 macrophages and mast cells become fragmented, and in the Treg cells and M2 macrophages they become elongated.…”

“…Mitochondria in the T effector cells, M1 macrophages and mast cells become fragmented, and in the Treg cells and M2 macrophages they become elongated. This phenomenon determines the regulatory function of mitochondrial morphology, because it is associated with their energy transformation -glycolysis occurs in the T effector lymphocytes and M1 macrophages, and oxidative phosphorylation and β-fatty acid oxidation in the Treg lymphocytes and M2 macrophages (Chelombitko et al, 2020).…”