Single-Walled Carbon Nanotubes Alter Cytochrome c Electron Transfer and Modulate Mitochondrial Function

Abstract

Single-walled carbon nanotubes (SWCNTs) are broadly used for various biomedical applications such as drug delivery, in vivo imaging and cancer photothermal therapy due to their unique physiochemical properties. However, once they enter the cells, the effects of SWCNTs to the intracellular organelles and macromolecules are not comprehensively understood. Cytochrome c (Cyt c), as a key component of the electron transport chain in mitochondria, plays an essential role in cellular energy consumption, growth and differentiation. In this study, we found the mitochondrial membrane potential (MMP) and mitochondrial oxygen uptake were greatly decreased in human epithelial KB cells treated with SWCNTs, which accompanies the reduction of Cyt c. SWCNTs deoxidized Cyt c in a pH dependent manner as evidenced by the appearance of a 550 nm characteristic absorption peak, which intensity increased as pH increase. Circular dichroism measurement confirmed the pH-dependent conformational change, which facilitated closer association of SWCNTs with the heme pocket of Cyt c and thus expedited the reduction of Cyt c. The electron transfer of Cyt c is also disturbed by SWCNTs, as measured with electron spin resonance spectroscopy. In conclusion, the redox activity of Cyt c was affected by SWCNTs treatment due to attenuated electron transfer and conformational change of Cyt c, which consequently changed mitochondrial respiration of SWCNTs treated cells. This work is significant to SWCNTs research because it provided novel understanding to the disruption of SWCNTs to the mitochondria and has important implications for biomedical applications of SWCNTs.

Plant nanobionics approach to augment photosynthesis and biochemical sensing

“…Together these results suggest that SWNTs are transported through the chloroplast membranes in a process driven by diffusion and spontaneous surface reaction. Consistent with our results, it has been reported that carboxylated SWNTs localize in mitochondria 24 ,…”

Lysosomal membrane permeabilization: Carbon nanohorn-induced reactive oxygen species generation and toxicity by this neglected mechanism

“…Cyt C plays an important role in electron transport by interacting with redox partners of complex III and complex IV. Ma et al (2012) reported that SWNT directly alter Cyt C electron transfer and modulate mitochondrial function. In this study, because the CNHs were not found in the mitochondria, it could be that the released cathepsins during the CNH-induced LMP caused the mitochondria certain respiratory chain disruption and induced ROS generation.…”

Aggregated single-walled carbon nanotubes attenuate the behavioural and neurochemical effects of methamphetamine in mice

“…In contrast to their wide implications, little is known about the biological effects of the SWNTs themselves. We and others have reported that low doses of SWNTs are neuroprotective in animal models of Alzheimer’s disease 4 and strokes 5 ; SWNTs were also reported to alter mitochondrial function and intracellular energy metabolism 6,7 . Strikingly, recent studies showed that nanoparticle-coated electrodes are highly sensitive and effective in the adsorption and oxidation of dopamine, largely through increasing the electroactive surface areas 8–10 .…”