Toxicity of polyhydroxylated fullerene to mitochondria.
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.
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.
Li-Yun
LY
Yang
Department of Chemistry, College of Chemistry and Environmental Engineering, Yangtze University, Jingzhou 434023, PR China.
Jia-Ling
JL
Gao
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.
Tian
T
Gao
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.
Ping
P
Dong
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.
Long
L
Ma
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.
Feng-Lei
FL
Jiang
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. Electronic address: yiliuchem@whu.edu.cn.
Yi
Y
Liu
D000818:Animals; D005260:Female; D037741:Fullerenes / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D017208:Rats, Wistar
D037741:Fullerenes; C108127:fullerenol
Isolated mitochondria; Mitochondrial membrane fluidity; Mitochondrial permeability transition; Polyhydroxylated fullerene