State Key Laboratory of Virology & Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, PR China.
Department of Chemistry, College of Chemistry and Environmental Engineering, Yangtze University, Jingzhou 434023, PR China.
J Hazard Mater. 2016 Jan 15;301:119-26. doi: 10.1016/j.jhazmat.2015.08.046. Epub 2015 Aug 28.
Mitochondrial dysfunction is considered as a crucial mechanism of nanomaterial toxicity. Herein, we investigated the effects of polyhydroxylated fullerene (C60(OH)44, fullerenol), a model carbon-based nanomaterial with high water solubility, on isolated mitochondria. Our study demonstrated that fullerenol enhanced the permeabilization of mitochondrial inner membrane to H(+) and K(+) and induced mitochondrial permeability transition (MPT). The fullerenol-induced swelling was dose-dependent and could be effectively inhibited by MPT inhibitors such as cyclosporin A (CsA), adenosine diphosphate (ADP), ruthenium red (RR) and ethylenediaminetetraacetic acid (EDTA). After treating the mitochondria with fullerenol, the mitochondrial membrane potential (MMP) was found collapsed in a concentration-independent manner. The fluorescence anisotropy of hematoporphyrin (HP) changed significantly with the addition of fullerenol, while that of 1,6-diphenyl-hexatriene (DPH) changed slightly. Moreover, a decrease of respiration state 3 and increase of respiration state 4 were observed when mitochondria were energized with complex II substrate succinate. The results of transmission electron microscopy (TEM) provided direct evidence that fullerenol damaged the mitochondrial ultrastructure. The investigations can provide comprehensive information to elucidate the possible toxic mechanism of fullerenols at subcellular level.
线粒体功能障碍被认为是纳米材料毒性的关键机制。在此，我们研究了具有高水溶性的模型碳基纳米材料——多羟基富勒烯（C60(OH)44，富勒醇）对分离线粒体的影响。我们的研究表明，富勒醇增强了线粒体内膜对 H(+)和 K(+)的通透性，并诱导了线粒体通透性转变（MPT）。富勒醇诱导的肿胀是剂量依赖性的，可以被 MPT 抑制剂如环孢菌素 A（CsA）、二磷酸腺苷（ADP）、钌红（RR）和乙二胺四乙酸（EDTA）有效抑制。在用富勒醇处理线粒体后，线粒体膜电位（MMP）以浓度非依赖性的方式发生崩溃。血卟啉（HP）的荧光各向异性随着富勒醇的加入而显著改变，而 1,6-二苯基-1,3,5-己三烯（DPH）的荧光各向异性则略有改变。此外，当用复合物 II 底物琥珀酸给线粒体供能时，观察到呼吸状态 3 的减少和呼吸状态 4 的增加。透射电子显微镜（TEM）的结果提供了直接证据，表明富勒醇破坏了线粒体的超微结构。这些研究可以提供全面的信息，以阐明富勒醇在亚细胞水平的可能毒性机制。
