SERS uncovers the link between conformation of cytochrome c heme and mitochondrial membrane potential

Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review

Autoren

  • Nadezda A. Brazhe
  • Evelina I. Nikelshparg
  • Adil A. Baizhumanov
  • Vera G. Grivennikova
  • Anna A. Semenova
  • Sergey M. Novikov
  • Valentyn S. Volkov
  • Aleksey V. Arsenin
  • Dmitry I. Yakubovsky
  • Andrey B. Evlyukhin
  • Zhanna V. Bochkova
  • Eugene A. Goodilin
  • Georgy V. Maksimov
  • Olga Sosnovtseva
  • Andrey B. Rubin

Organisationseinheiten

Externe Organisationen

  • Lomonosov Moscow State University
  • Moscow Institute of Physics and Technology
  • Skolkovo Innovation Center
  • Russian Academy of Sciences (RAS)
  • National University of Science and Technology MISIS
  • Københavns Universitet
Forschungs-netzwerk anzeigen

Details

OriginalspracheEnglisch
Seiten (von - bis)133-144
Seitenumfang12
FachzeitschriftFree Radical Biology and Medicine
Jahrgang196
Frühes Online-Datum14 Jan. 2023
PublikationsstatusVeröffentlicht - 20 Feb. 2023

Abstract

The balance between the mitochondrial respiratory chain activity and the cell's needs in ATP ensures optimal cellular function. Cytochrome c is an essential component of the electron transport chain (ETC), which regulates ETC activity, oxygen consumption, ATP synthesis and can initiate apoptosis. The impact of conformational changes in cytochrome c on its function is not understood for the lack of access to these changes in intact mitochondria. We have developed a novel sensor that uses unique properties of label-free surface-enhanced Raman spectroscopy (SERS) to identify conformational changes in heme of cytochrome c and to elucidate their role in functioning mitochondria. We have verified that molecule bond vibrations assessed by SERS are a reliable indicator of the heme conformation during changes in the inner mitochondrial membrane potential and ETC activity. We have demonstrated that cytochrome c heme reversibly switches between planar and ruffled conformations in response to the inner mitochondrial membrane potential (ΔΨ) and H+ concentration in the intermembrane space. This regulates the efficiency of the mitochondrial respiratory chain, thus, adjusting the mitochondrial respiration to the cell's consumption of ATP and the overall activity. We have found that under hypertensive conditions cytochrome c heme loses its sensitivity to ΔΨ that can affect the regulation of ETC activity. The ability of the proposed SERS-based sensor to track mitochondrial function opens broad perspectives in cell bioenergetics.

ASJC Scopus Sachgebiete

Zitieren

SERS uncovers the link between conformation of cytochrome c heme and mitochondrial membrane potential. / Brazhe, Nadezda A.; Nikelshparg, Evelina I.; Baizhumanov, Adil A. et al.
in: Free Radical Biology and Medicine, Jahrgang 196, 20.02.2023, S. 133-144.

Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review

Brazhe, NA, Nikelshparg, EI, Baizhumanov, AA, Grivennikova, VG, Semenova, AA, Novikov, SM, Volkov, VS, Arsenin, AV, Yakubovsky, DI, Evlyukhin, AB, Bochkova, ZV, Goodilin, EA, Maksimov, GV, Sosnovtseva, O & Rubin, AB 2023, 'SERS uncovers the link between conformation of cytochrome c heme and mitochondrial membrane potential', Free Radical Biology and Medicine, Jg. 196, S. 133-144. https://doi.org/10.1016/j.freeradbiomed.2023.01.013
Brazhe, N. A., Nikelshparg, E. I., Baizhumanov, A. A., Grivennikova, V. G., Semenova, A. A., Novikov, S. M., Volkov, V. S., Arsenin, A. V., Yakubovsky, D. I., Evlyukhin, A. B., Bochkova, Z. V., Goodilin, E. A., Maksimov, G. V., Sosnovtseva, O., & Rubin, A. B. (2023). SERS uncovers the link between conformation of cytochrome c heme and mitochondrial membrane potential. Free Radical Biology and Medicine, 196, 133-144. https://doi.org/10.1016/j.freeradbiomed.2023.01.013
Brazhe NA, Nikelshparg EI, Baizhumanov AA, Grivennikova VG, Semenova AA, Novikov SM et al. SERS uncovers the link between conformation of cytochrome c heme and mitochondrial membrane potential. Free Radical Biology and Medicine. 2023 Feb 20;196:133-144. Epub 2023 Jan 14. doi: 10.1016/j.freeradbiomed.2023.01.013
Brazhe, Nadezda A. ; Nikelshparg, Evelina I. ; Baizhumanov, Adil A. et al. / SERS uncovers the link between conformation of cytochrome c heme and mitochondrial membrane potential. in: Free Radical Biology and Medicine. 2023 ; Jahrgang 196. S. 133-144.
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title = "SERS uncovers the link between conformation of cytochrome c heme and mitochondrial membrane potential",
abstract = "The balance between the mitochondrial respiratory chain activity and the cell's needs in ATP ensures optimal cellular function. Cytochrome c is an essential component of the electron transport chain (ETC), which regulates ETC activity, oxygen consumption, ATP synthesis and can initiate apoptosis. The impact of conformational changes in cytochrome c on its function is not understood for the lack of access to these changes in intact mitochondria. We have developed a novel sensor that uses unique properties of label-free surface-enhanced Raman spectroscopy (SERS) to identify conformational changes in heme of cytochrome c and to elucidate their role in functioning mitochondria. We have verified that molecule bond vibrations assessed by SERS are a reliable indicator of the heme conformation during changes in the inner mitochondrial membrane potential and ETC activity. We have demonstrated that cytochrome c heme reversibly switches between planar and ruffled conformations in response to the inner mitochondrial membrane potential (ΔΨ) and H+ concentration in the intermembrane space. This regulates the efficiency of the mitochondrial respiratory chain, thus, adjusting the mitochondrial respiration to the cell's consumption of ATP and the overall activity. We have found that under hypertensive conditions cytochrome c heme loses its sensitivity to ΔΨ that can affect the regulation of ETC activity. The ability of the proposed SERS-based sensor to track mitochondrial function opens broad perspectives in cell bioenergetics.",
keywords = "Cytochrome c, Electron transport chain, Heme, Mitochondria, Surface-enhanced Raman spectroscopy",
author = "Brazhe, {Nadezda A.} and Nikelshparg, {Evelina I.} and Baizhumanov, {Adil A.} and Grivennikova, {Vera G.} and Semenova, {Anna A.} and Novikov, {Sergey M.} and Volkov, {Valentyn S.} and Arsenin, {Aleksey V.} and Yakubovsky, {Dmitry I.} and Evlyukhin, {Andrey B.} and Bochkova, {Zhanna V.} and Goodilin, {Eugene A.} and Maksimov, {Georgy V.} and Olga Sosnovtseva and Rubin, {Andrey B.}",
note = "Funding information: This research has been supported by the Interdisciplinary Scientific and Educational School of Moscow University “Molecular Technologies of the Living Systems and Synthetic Biology”. NAB acknowledges support from Russian Foundation for Basic Research (RFBR, grant number 20-04-01011а), EIN acknowledges support from Russian Science foundation (RSF, grant number 21-74-00026), AAS acknowledges support from Russian Science Foundation (RSF, grant number 20-73-00257). AVA and SMN acknowledge support ",
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Download

TY - JOUR

T1 - SERS uncovers the link between conformation of cytochrome c heme and mitochondrial membrane potential

AU - Brazhe, Nadezda A.

AU - Nikelshparg, Evelina I.

AU - Baizhumanov, Adil A.

AU - Grivennikova, Vera G.

AU - Semenova, Anna A.

AU - Novikov, Sergey M.

AU - Volkov, Valentyn S.

AU - Arsenin, Aleksey V.

AU - Yakubovsky, Dmitry I.

AU - Evlyukhin, Andrey B.

AU - Bochkova, Zhanna V.

AU - Goodilin, Eugene A.

AU - Maksimov, Georgy V.

AU - Sosnovtseva, Olga

AU - Rubin, Andrey B.

N1 - Funding information: This research has been supported by the Interdisciplinary Scientific and Educational School of Moscow University “Molecular Technologies of the Living Systems and Synthetic Biology”. NAB acknowledges support from Russian Foundation for Basic Research (RFBR, grant number 20-04-01011а), EIN acknowledges support from Russian Science foundation (RSF, grant number 21-74-00026), AAS acknowledges support from Russian Science Foundation (RSF, grant number 20-73-00257). AVA and SMN acknowledge support

PY - 2023/2/20

Y1 - 2023/2/20

N2 - The balance between the mitochondrial respiratory chain activity and the cell's needs in ATP ensures optimal cellular function. Cytochrome c is an essential component of the electron transport chain (ETC), which regulates ETC activity, oxygen consumption, ATP synthesis and can initiate apoptosis. The impact of conformational changes in cytochrome c on its function is not understood for the lack of access to these changes in intact mitochondria. We have developed a novel sensor that uses unique properties of label-free surface-enhanced Raman spectroscopy (SERS) to identify conformational changes in heme of cytochrome c and to elucidate their role in functioning mitochondria. We have verified that molecule bond vibrations assessed by SERS are a reliable indicator of the heme conformation during changes in the inner mitochondrial membrane potential and ETC activity. We have demonstrated that cytochrome c heme reversibly switches between planar and ruffled conformations in response to the inner mitochondrial membrane potential (ΔΨ) and H+ concentration in the intermembrane space. This regulates the efficiency of the mitochondrial respiratory chain, thus, adjusting the mitochondrial respiration to the cell's consumption of ATP and the overall activity. We have found that under hypertensive conditions cytochrome c heme loses its sensitivity to ΔΨ that can affect the regulation of ETC activity. The ability of the proposed SERS-based sensor to track mitochondrial function opens broad perspectives in cell bioenergetics.

AB - The balance between the mitochondrial respiratory chain activity and the cell's needs in ATP ensures optimal cellular function. Cytochrome c is an essential component of the electron transport chain (ETC), which regulates ETC activity, oxygen consumption, ATP synthesis and can initiate apoptosis. The impact of conformational changes in cytochrome c on its function is not understood for the lack of access to these changes in intact mitochondria. We have developed a novel sensor that uses unique properties of label-free surface-enhanced Raman spectroscopy (SERS) to identify conformational changes in heme of cytochrome c and to elucidate their role in functioning mitochondria. We have verified that molecule bond vibrations assessed by SERS are a reliable indicator of the heme conformation during changes in the inner mitochondrial membrane potential and ETC activity. We have demonstrated that cytochrome c heme reversibly switches between planar and ruffled conformations in response to the inner mitochondrial membrane potential (ΔΨ) and H+ concentration in the intermembrane space. This regulates the efficiency of the mitochondrial respiratory chain, thus, adjusting the mitochondrial respiration to the cell's consumption of ATP and the overall activity. We have found that under hypertensive conditions cytochrome c heme loses its sensitivity to ΔΨ that can affect the regulation of ETC activity. The ability of the proposed SERS-based sensor to track mitochondrial function opens broad perspectives in cell bioenergetics.

KW - Cytochrome c

KW - Electron transport chain

KW - Heme

KW - Mitochondria

KW - Surface-enhanced Raman spectroscopy

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DO - 10.1016/j.freeradbiomed.2023.01.013

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JO - Free Radical Biology and Medicine

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SN - 0891-5849

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