title: Mitochondrial proteomic analysis reveals the molecular mechanisms underlying reproductive toxicity of zearalenone in MLTC-1 cells.
abstract: Zearalenone (ZEA), a Fusarium mycotoxin that contaminates cereal crops worldwide, has been shown to affect the male reproductive system and trigger reactive oxygen species (ROS) generation. However, the mechanisms of its toxicity have not been fully understood. Because mitochondrion is a key organelle involved in producing ROS and generating metabolic intermediates for biosynthesis, an iTRAQ-based mitoproteomics approach was employed to identify the molecular mechanism of zearalenone toxicity using mitochondria of mouse Leydig tumor cells (MLTC-1). A total of 2014 nonredundant proteins were identified, among which 1401 proteins (69.56%) were overlapped. There were 52 differentially expressed proteins in response to ZEA, and they were primarily involved in energy metabolism, molecular transport and endocrine-related functions. Consistent with mitochondrial proteomic analysis, the ATP and intracellular Ca(2+) levels increased after ZEA treatment. The results suggest that lipid metabolism changed significantly after low-dose ZEA exposure, resulting in two alterations. One is the increase in energy production through promoted fatty acid uptake and β-oxidation, along with excessive oxidative stress; the other is an inhibition of steroidogenesis and esterification, possibly resulting in reduced hormone secretion. A hypothetical model of ZEA-induced mitochondrial damage is proposed to provide a framework for the mechanism of ZEA toxicity.
authors: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, People's Republic of China.
authors: Yuzhe
authors: Y
authors: Li
authors: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, People's Republic of China.
authors: Boyang
authors: B
authors: Zhang
authors: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, People's Republic of China.
authors: Kunlun
authors: K
authors: Huang
authors: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, People's Republic of China.
authors: Xiaoyun
authors: X
authors: He
authors: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, People's Republic of China.
authors: YunBo
authors: Y
authors: Luo
authors: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, People's Republic of China.
authors: Rui
authors: R
authors: Liang
authors: Department of Animal Physiology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors: Haoshu
authors: H
authors: Luo
authors: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, People's Republic of China.
authors: Xiao Li
authors: XL
authors: Shen
authors: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, People's Republic of China. Electronic address: xuwentao@cau.edu.cn.
authors: Wentao
authors: W
authors: Xu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D030562:Databases, Protein; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D007984:Leydig Cell Tumor / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D040901:Proteomics / Q000379:methods*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects*; D053719:Tandem Mass Spectrometry; D013739:Testosterone / Q000378:metabolism; D015025:Zearalenone / Q000633:toxicity*
chemical_list: D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D013739:Testosterone; D015025:Zearalenone; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: Endocrine disorder; Fatty acid oxidation; Lipid metabolism; Mitoproteomics; Mouse Leydig tumor cells; Reproductive toxicity; Zearalenone