Multiplexed quantitative evaluation on mitochondrial toxicity of tris (2,3-dibromopropyl) phosphate in hepatocyte

Ecotoxicology and Environmental Safety

Xiaowen Li¹  Dezhao Lu¹  Yifei Le¹  Xiaochun Ma²  Ying Liu²  Cui Wang²  Hang Chen² 

[1] School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, People’s Republic of China;Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, People’s Republic of China;

关键词: (2;    3-dibromopropyl) phosphate;    Mitochondria dynamics;    Mitochondria dysfunction;    Lipid accumulation;   

DOI  :  

来源: DOAJ

【 摘 要 】

The frequent detection of (2,3-dibromopropyl) phosphate (TDBPP) in environment has led to a consistent risk to organisms. However, little is known about the toxicity of TDBPP exclusive for its carcinogen. Mitochondrion that tightly relates to adverse outcomes once deteriorated is referred as a target of environmental pollutants. Here, we investigated the role of mitochondrial abnormality in development of cellular pathobiology especially lipid deposition when response to TDBPP in mitochondria-rich hepatocyte (AML12) at the same order of magnitude as the environmental concentrations (10−6 mol/L or below) via multiplexed quantitative high content analytic system. The present study claimed TDBPP shifted mitochondria from fusion morphology to fission phenotype charactering by less mitochondrial networks, larger mitochondrial areas and shorter branch length at 10−7 mol/L or above. This dynamic imbalance was triggered by high levels of fis and drp1 genes when treated with TDBPP. The deformation caused by TDBPP reciprocally influenced biogenesis through PGC1α and electron transport chains via ectopic expression of genes encoding for mitochondria complex I and III subunits. Accordingly, we observed high mitoROS level and low mitochondria membrane potential. Consequently, cells contained those abnormal mitochondria were predisposed to accumulating lipids after exposure to TDBPP. Here we showed that TDBPP deteriorated mitochondrial morphology and function, which may induce lipid generation. As for a banned while still emerged contaminant, our study also claimed further exploration on the non-carcinogenic toxicity of TDBPP.

【 授权许可】

Unknown