Electron transfer through the mitochondrial electron transport chain (ETC) can be critically blocked by the dysfunction of protein complexes. Redox-active molecules have been used to mediate the electron transfer in place of the dysfunctional complexes; however, they are limited to replacing complex I and are known to be toxic. Here we report artificial mitochondrial electron transfer pathways that enhance ETC activity by exploiting inner-membrane-bound gold nanoparticles (GNPs) as efficient electron transfer mediators. The hybridization of mitochondria with GNPs, driven by electrostatic interaction, is successfully visualized in real time at the level of a single mitochondrion. By observing quantized quenching dips via plasmon resonance energy transfer, we reveal that the hybridized GNPs are bound to the inner membrane of mitochondria irrespective of the presence of the outer membrane. The ETC activity of mitochondria with GNPs such as membrane potential, oxygen consumption, and ATP production is remarkably increased in vitro.
Bibliographical noteFunding Information:
This work was supported by the Mid-Career Researcher Support Program (Grant NRF-2020R1A2C3012167) and C1 Gas Refinery Program (Grant NRF-2018M3D3A1A01055759) of the National Research Foundation of Korea (NRF) by the Ministry of Science and ICT, and the Basic Science Research Program (Grant NRF-2016R1A6A1A03012845) of the NRF by the Ministry of Education (T.K.). This research was supported by the Air Force Office of Scientific Research Grants (Grant AFOSR FA2386-20-1-4060) (T.K. and L.P.L). This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant HV22C0069) (M.-L.C.). This work was also supported by NRF grant funded by the Korea government (MIST) (Grant NRF-2021R1A2C1008497) (J.S.W.) The authors thank Prof. Dongeun Huh and Prof. Kidong Park for helpful discussions.
© 2022 American Chemical Society. All rights reserved.
- ATP production
- electron transport chain
- gold nanoparticle
- plasmon resonance energy transfer