Details
Original language | English |
---|---|
Pages (from-to) | 133-144 |
Number of pages | 12 |
Journal | Free Radical Biology and Medicine |
Volume | 196 |
Early online date | 14 Jan 2023 |
Publication status | Published - 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.
Keywords
- Cytochrome c, Electron transport chain, Heme, Mitochondria, Surface-enhanced Raman spectroscopy
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Medicine(all)
- Physiology (medical)
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In: Free Radical Biology and Medicine, Vol. 196, 20.02.2023, p. 133-144.
Research output: Contribution to journal › Article › Research › peer review
}
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
UR - http://www.scopus.com/inward/record.url?scp=85147375576&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2023.01.013
DO - 10.1016/j.freeradbiomed.2023.01.013
M3 - Article
C2 - 36649901
AN - SCOPUS:85147375576
VL - 196
SP - 133
EP - 144
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -