Picturing Molecular Environmental Health From Mitochondria

Abstract

triphosphate IntroductionHuman diseases are determined by both genetic and environmental risk factors. A recent investigation indicates that environmental factors contribute to about 80% of the 102 diseases and injuries listed by the World Health Organization (WHO) for the year 2002, and account for 24% of the global burden of disease [1]. These data clearly indicate a key role of environmental factors in human health. Modern molecular and cellular studies have revealed a great detail of normal and disease biological processes at the molecular level; however, the molecular mechanisms by which environmental risk factors cause human diseases are still not well understood. An in-depth understanding of these molecular mechanisms is the prerequisite for the design of new strategies of prevention and therapy, and requires intensive investigations in the cutting edge field -Molecular Environmental Health. In this essay, the author uses the organelle mitochondria as an example to connect Molecular Biology and Environmental Health from available literature, to demonstrate the level of clarity of scientific understanding we can achieve by studying environmental health at the molecular and cellular levels. Recent Advances in Mitochondrial BiologyAs an important cellular organelle, mitochondria are known for producing adenosine triphosphate (ATP), buffering calcium and participating apoptosis. Moreover, mitochondria host a variety of metabolic processes, such as the tricarboxylic acid (TCA) cycle, fatty acid beta-oxidation, and synthesis of lipid, steroid, heme and ironsulfur clusters. In the past decades, several significant progresses have been made which have expanded our conventional understanding of the function and regulation of mitochondria.One progress is that mitochondria modulate cellular signal pathways by generating reactive oxygen species (ROS). ROS are oxygencontaining, highly chemically reactive molecules, including superoxide anion, hydroxyl radical and hydrogen peroxide. Mitochondria generate superoxide from oxygen at the site of the mitochondrial electron transport chain as an intrinsic product of oxidative phosphorylation. Traditionally, ROS are considered toxic as high level of ROS causes oxidative damage: protein oxidation, lipid peroxidation and DNA mutation. However, numerous studies have demonstrated that moderate or low levels of ROS are an important cellular signaling transducer in cell proliferation, differentiation and migration [2][3][4][5][6]. In fact, mitochondria-generated superoxide is converted to hydrogen peroxide. Hydrogen peroxide is a signaling messenger that can travel for a distance within the cell to oxidize key protein residues such as cysteines, resulting in change of the conformation or activity of kinases, phosphatases or transcription factors in various cellular signaling pathways. These redox-sensitive signaling pathways, such as the mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/Erk), nuclear factor erythroid-derived 2-related factor 2 (Nrf-2), c...