Proton tunneling allows a proton-coupled electron transfer process in the cancer cell
- Author
- Tong Zhang, Arindam Ghosh, Lisa Behringer-Pliess, Lata Chouhan, Ana V. Cunha, Remco Havenith (UGent) , Eugenia Butkevich, Lei Zhang, Olalla Vázquez, Elke Debroye, Jörg Enderlein and Shoubhik Das
- Organization
- Abstract
- Proton-coupled electron transfer (PCET) is a fundamental redox process and has clear advantages in selectively activating challenging C-H bonds in many biological processes. Intrigued by this activation process, we aimed to develop a facile PCET process in cancer cells by modulating proton tunneling. This approach should lead to the design of an alternative photodynamic therapy (PDT) that depletes the mitochondrial electron transport chain (ETC), the key redox regulator in cancer cells under hypoxia. To observe this depletion process in the cancer cell, we monitored the oxidative-stress-induced depolarization of mitochondrial inner membrane potential (MMP) using fluorescence lifetime imaging microscopy (FLIM). Typically, increasing metabolic stress of cancer cells is reflected in a nontrivial change in the fluorophore's fluorescence lifetime. After 30 min of irradiation, we observed a shift in the mean lifetime value and a drastic drop in overall fluorescence signal. In addition, our PCET strategy resulted in drastic reorganization of mitochondrial morphology from tubular to vesicle-like and causing an overall depletion of intact mitochondria in the hypodermis of C. elegans. These observations confirmed that PCET promoted ROS-induced oxidative stress. Finally, we gained a clear understanding of the proton tunneling effect in the PCET process through photoluminescence experiments and DFT calculations.
- Keywords
- proton tunneling, proton-coupled electron transfer, photodynamic therapy, metal free, fluorenonederivatives, PHOTODYNAMIC THERAPY, CYTOCHROME-C
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01JN3B0T4NYX8SPEP9XENSWA9S
- MLA
- Zhang, Tong, et al. “Proton Tunneling Allows a Proton-Coupled Electron Transfer Process in the Cancer Cell.” JACS AU, vol. 4, no. 12, 2024, pp. 4856–65, doi:10.1021/jacsau.4c00815.
- APA
- Zhang, T., Ghosh, A., Behringer-Pliess, L., Chouhan, L., Cunha, A. V., Havenith, R., … Das, S. (2024). Proton tunneling allows a proton-coupled electron transfer process in the cancer cell. JACS AU, 4(12), 4856–4865. https://doi.org/10.1021/jacsau.4c00815
- Chicago author-date
- Zhang, Tong, Arindam Ghosh, Lisa Behringer-Pliess, Lata Chouhan, Ana V. Cunha, Remco Havenith, Eugenia Butkevich, et al. 2024. “Proton Tunneling Allows a Proton-Coupled Electron Transfer Process in the Cancer Cell.” JACS AU 4 (12): 4856–65. https://doi.org/10.1021/jacsau.4c00815.
- Chicago author-date (all authors)
- Zhang, Tong, Arindam Ghosh, Lisa Behringer-Pliess, Lata Chouhan, Ana V. Cunha, Remco Havenith, Eugenia Butkevich, Lei Zhang, Olalla Vázquez, Elke Debroye, Jörg Enderlein, and Shoubhik Das. 2024. “Proton Tunneling Allows a Proton-Coupled Electron Transfer Process in the Cancer Cell.” JACS AU 4 (12): 4856–4865. doi:10.1021/jacsau.4c00815.
- Vancouver
- 1.Zhang T, Ghosh A, Behringer-Pliess L, Chouhan L, Cunha AV, Havenith R, et al. Proton tunneling allows a proton-coupled electron transfer process in the cancer cell. JACS AU. 2024;4(12):4856–65.
- IEEE
- [1]T. Zhang et al., “Proton tunneling allows a proton-coupled electron transfer process in the cancer cell,” JACS AU, vol. 4, no. 12, pp. 4856–4865, 2024.
@article{01JN3B0T4NYX8SPEP9XENSWA9S,
abstract = {{Proton-coupled electron transfer (PCET) is a fundamental redox process and has clear advantages in selectively activating challenging C-H bonds in many biological processes. Intrigued by this activation process, we aimed to develop a facile PCET process in cancer cells by modulating proton tunneling. This approach should lead to the design of an alternative photodynamic therapy (PDT) that depletes the mitochondrial electron transport chain (ETC), the key redox regulator in cancer cells under hypoxia. To observe this depletion process in the cancer cell, we monitored the oxidative-stress-induced depolarization of mitochondrial inner membrane potential (MMP) using fluorescence lifetime imaging microscopy (FLIM). Typically, increasing metabolic stress of cancer cells is reflected in a nontrivial change in the fluorophore's fluorescence lifetime. After 30 min of irradiation, we observed a shift in the mean lifetime value and a drastic drop in overall fluorescence signal. In addition, our PCET strategy resulted in drastic reorganization of mitochondrial morphology from tubular to vesicle-like and causing an overall depletion of intact mitochondria in the hypodermis of C. elegans. These observations confirmed that PCET promoted ROS-induced oxidative stress. Finally, we gained a clear understanding of the proton tunneling effect in the PCET process through photoluminescence experiments and DFT calculations.}},
author = {{Zhang, Tong and Ghosh, Arindam and Behringer-Pliess, Lisa and Chouhan, Lata and Cunha, Ana V. and Havenith, Remco and Butkevich, Eugenia and Zhang, Lei and Vázquez, Olalla and Debroye, Elke and Enderlein, Jörg and Das, Shoubhik}},
issn = {{2691-3704}},
journal = {{JACS AU}},
keywords = {{proton tunneling,proton-coupled electron transfer,photodynamic therapy,metal free,fluorenonederivatives,PHOTODYNAMIC THERAPY,CYTOCHROME-C}},
language = {{eng}},
number = {{12}},
pages = {{4856--4865}},
title = {{Proton tunneling allows a proton-coupled electron transfer process in the cancer cell}},
url = {{http://doi.org/10.1021/jacsau.4c00815}},
volume = {{4}},
year = {{2024}},
}
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