IDH2: A novel biomarker for environmental exposure in blood circulatory system disorders

Abstract

As the risk of harmful environmental exposure is increasing, it is important to find suitable targets for the diagnosis and treatment of the diseases caused. Isocitrate dehydrogenase 2 (IDH2) is an enzyme located in the mitochondria; it plays an important role in numerous cell processes, including maintaining redox homeostasis, participating in the tricarboxylic acid cycle and indirectly taking part in the transmission of the oxidative respiratory chain. IDH2 mutations promote progression in acute myeloid leukemia, glioma and other diseases. The present review mainly summarizes the role and mechanism of IDH2 with regard to the biological effects, such as the mitophagy and apoptosis of animal or human cells, caused by environmental pollution such as radiation, heavy metals and other environmental exposure factors. The possible mechanisms of these biological effects are described in terms of IDH2 expression, reduced nicotine adenine dinucleotide phosphate content and reactive oxygen species level, among other variables. The impact of environmental pollution on human health is increasingly attracting attention. IDH2 may therefore become useful as a potential diagnostic and therapeutic target for environmental exposure-induced diseases.

Keywords: exposure damage; hematopoietic diseases; isocitrate dehydrogenase 2; pathological processes; reactive oxygen species; regulatory factors.

Figure 1.

IDH family participates in metabolic processes and epigenetic regulation. (A) α-KG and 2-HG are involved in epigenetic modification. (B) Tricarboxylic acid cycle in the mitochondria. The isocitric acid turns into α-KG via the IDH enzyme family. The IDH enzyme family catalyze the oxidative decarboxylation of isocitrate and therefore play key roles in the Krebs cycle. (C) Glycolysis of glucose in the cytoplasm. G-6-P, glucose-6-phophate; F-6-P, fructose-6-phosphate; F-1,6-2P, 1,6-fructose-diphosphate; α-KG, α-ketoglutarate; 2-HG, 2-hydroxyglutarate; IDH, isocitrate dehydrogenase; Gln, Glutamine; Glu, glutamic acid; NADH, nicotinamide adenine dinucleotide; Jmjc, jumonji C.

Figure 2.

Pathway diagram for the regulation of IDH2. Internal or external factors (such as radiation and metals in the environment) cause changes in the expression or activity of IDH2, resulting in skin damage and mitochondrial autophagy, among others. MPP+, methyl-4-phenylpyridinium; TET, methylcytosine dioxygenase; α-KG, α-ketoglutarate; 5-hmc, 5-hydroxymethylcytosine; mtROS, mitochondria reactive oxygen species; MDA, malondialdehyde; As3+, arsenic; UV, ultraviolet; GPX4, glutathione peroxidase 4; GSH, glutathione; SIRT3, sirtuin 3; IDH2, isocitrate dehydrogenase 2.