Respiratory uncoupling by increased H+ or K+ flux is beneficial for heart mitochondrial turnover of reactive oxygen species but not for permeability transition
Morota, Saori LU ; Piel, Sarah LU
and Hansson, Magnus
LU
(2013)
In BMC Cell Biology
14.
- Abstract
- Background: Ischemic preconditioning has been proposed to involve changes in mitochondrial H+ and K+ fluxes, in particular through activation of uncoupling proteins and ATP-sensitive K+ channels (MitoK(ATP)). The objectives of the present study were to explore how increased H+ and K+ fluxes influence heart mitochondrial physiology with regard to production and scavenging of reactive oxygen species (ROS), volume changes and resistance to calcium-induced mitochondrial permeability transition (mPT). Results: Isolated rat heart mitochondria were exposed to a wide concentration range of the protonophore CCCP or the potassium ionophore valinomycin to induce increased H+ and K+ conductance, respectively. Simultaneous monitoring of mitochondrial... (More)
- Background: Ischemic preconditioning has been proposed to involve changes in mitochondrial H+ and K+ fluxes, in particular through activation of uncoupling proteins and ATP-sensitive K+ channels (MitoK(ATP)). The objectives of the present study were to explore how increased H+ and K+ fluxes influence heart mitochondrial physiology with regard to production and scavenging of reactive oxygen species (ROS), volume changes and resistance to calcium-induced mitochondrial permeability transition (mPT). Results: Isolated rat heart mitochondria were exposed to a wide concentration range of the protonophore CCCP or the potassium ionophore valinomycin to induce increased H+ and K+ conductance, respectively. Simultaneous monitoring of mitochondrial respiration and calcium retention capacity (CRC) demonstrated that the relative increase in respiration caused by valinomycin or CCCP correlated with a decrease in CRC, and that no level of respiratory uncoupling was associated with enhanced resistance to mPT. Mitochondria suspended in hyperosmolar buffer demonstrated a dose-dependent reduction in CRC with increasing osmolarity. However, mitochondria in hypoosmolar buffer to increase matrix volume did not display increased CRC. ROS generation was reduced by both K+- and H+-mediated respiratory uncoupling. The ability of heart mitochondria to detoxify H2O2 was substantially greater than the production rate. The H2O2 detoxification was dependent on respiratory substrates and was dramatically decreased following calcium-induced mPT, but was unaffected by uncoupling via increased K+ and H+ conductance. Conclusion: It is concluded that respiratory uncoupling is not directly beneficial to rat heart mitochondrial resistance to calcium overload irrespective of whether H+ or K+ conductance is increased. The negative effects of respiratory uncoupling thus probably outweigh the reduction in ROS generation and a potential positive effect by increased matrix volume, resulting in a net sensitization of heart mitochondria to mPT activation. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4172547
- author
- Morota, Saori
LU
; Piel, Sarah
LU
and Hansson, Magnus
LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Ischemic preconditioning, Mitochondrial permeability transition, Potassium channels, Respiratory uncoupling, Reactive oxygen species
- in
- BMC Cell Biology
- volume
- 14
- article number
- 40
- publisher
- BioMed Central (BMC)
- external identifiers
-
- wos:000325083200001
- scopus:84884323953
- pmid:24053891
- ISSN
- 1471-2121
- DOI
- 10.1186/1471-2121-14-40
- language
- English
- LU publication?
- yes
- id
- 0291e30f-db60-4228-8296-9444900e444d (old id 4172547)
- date added to LUP
- 2016-04-01 14:36:42
- date last changed
- 2024-01-10 06:10:45
@article{0291e30f-db60-4228-8296-9444900e444d,
abstract = {{Background: Ischemic preconditioning has been proposed to involve changes in mitochondrial H+ and K+ fluxes, in particular through activation of uncoupling proteins and ATP-sensitive K+ channels (MitoK(ATP)). The objectives of the present study were to explore how increased H+ and K+ fluxes influence heart mitochondrial physiology with regard to production and scavenging of reactive oxygen species (ROS), volume changes and resistance to calcium-induced mitochondrial permeability transition (mPT). Results: Isolated rat heart mitochondria were exposed to a wide concentration range of the protonophore CCCP or the potassium ionophore valinomycin to induce increased H+ and K+ conductance, respectively. Simultaneous monitoring of mitochondrial respiration and calcium retention capacity (CRC) demonstrated that the relative increase in respiration caused by valinomycin or CCCP correlated with a decrease in CRC, and that no level of respiratory uncoupling was associated with enhanced resistance to mPT. Mitochondria suspended in hyperosmolar buffer demonstrated a dose-dependent reduction in CRC with increasing osmolarity. However, mitochondria in hypoosmolar buffer to increase matrix volume did not display increased CRC. ROS generation was reduced by both K+- and H+-mediated respiratory uncoupling. The ability of heart mitochondria to detoxify H2O2 was substantially greater than the production rate. The H2O2 detoxification was dependent on respiratory substrates and was dramatically decreased following calcium-induced mPT, but was unaffected by uncoupling via increased K+ and H+ conductance. Conclusion: It is concluded that respiratory uncoupling is not directly beneficial to rat heart mitochondrial resistance to calcium overload irrespective of whether H+ or K+ conductance is increased. The negative effects of respiratory uncoupling thus probably outweigh the reduction in ROS generation and a potential positive effect by increased matrix volume, resulting in a net sensitization of heart mitochondria to mPT activation.}},
author = {{Morota, Saori and Piel, Sarah and Hansson, Magnus}},
issn = {{1471-2121}},
keywords = {{Ischemic preconditioning; Mitochondrial permeability transition; Potassium channels; Respiratory uncoupling; Reactive oxygen species}},
language = {{eng}},
publisher = {{BioMed Central (BMC)}},
series = {{BMC Cell Biology}},
title = {{Respiratory uncoupling by increased H+ or K+ flux is beneficial for heart mitochondrial turnover of reactive oxygen species but not for permeability transition}},
url = {{https://lup.lub.lu.se/search/files/4067673/4610157.pdf}},
doi = {{10.1186/1471-2121-14-40}},
volume = {{14}},
year = {{2013}},
}