Respiratory uncoupling by increased H+ or K+ flux is beneficial for heart mitochondrial turnover of reactive oxygen species but not for permeability transition

BMC Cell Biology

Magnus J Hansson¹  Sarah Piel²  Saori Morota³ 

[1]Department of Clinical Physiology, Skåne University Hospital & Lund University, Lund, Sweden

[2]Mitochondrial Pathophysiology Unit, Lund University, Lund, Sweden

[3]Department of Anesthesiology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan

关键词: Reactive oxygen species;    Respiratory uncoupling;    Potassium channels;    Mitochondrial permeability transition;    Ischemic preconditioning;   

Others  :  855143
DOI  :  10.1186/1471-2121-14-40

 received in 2013-06-04, accepted in 2013-09-16,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Morota et al.; licensee BioMed Central Ltd.

【 图 表 】

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