Adenosine Triphosphate Synthesis Coupled to K
            <sup>+</sup>
            Influx in Mitochondria

Kinnally, Kathleen W.; Tedeschi, Henry

doi:10.1126/science.6281882

Cited by 7 publications

(3 citation statements)

References 27 publications

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“…Valinomycin is an effective K + ionophore which facilitates K + flux across the mitochondrial membrane, and is an established tool for studying the consequences of increased K + conductance in mitochondria (Kinnally & Tedeschi, 1982; Holmuhamedov, 1986). Here, much like potassium channel openers, valinomycin also promoted Ca 2+ release from pre‐loaded mitochondria (Fig.…”

Section: Resultsmentioning

confidence: 99%

ATP‐sensitive K⁺ channel openers prevent Ca²⁺ overload in rat cardiac mitochondria

Holmuhamedov

Wang

Terzic

1999

The Journal of Physiology

328

218

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Mitochondrial dysfunction, secondary to excessive accumulation of Ca2+, has been implicated in cardiac injury. We here examined the action of potassium channel openers on mitochondrial Ca2+ homeostasis, as these cardioprotective ion channel modulators have recently been shown to target a mitochondrial ATP‐sensitive K+ channel. In isolated cardiac mitochondria, diazoxide and pinacidil decreased the rate and magnitude of Ca2+ uptake into the mitochondrial matrix with an IC50 of 65 and 128 μm, respectively. At all stages of Ca2+ uptake, the potassium channel openers depolarized the mitochondrial membrane thereby reducing Ca2+ influx through the potential‐dependent mitochondrial uniporter. Diazoxide and pinacidil, in a concentration‐dependent manner, also activated release of Ca2+ from mitochondria. This was prevented by cyclosporin A, an inhibitor of Ca2+ release through the mitochondrial permeability transition pore. Replacement of extramitochondrial K+ with mannitol abolished the effects of diazoxide and pinacidil on mitochondrial Ca2+, while the K+ ionophore valinomycin mimicked the effects of the potassium channel openers. ATP and ADP, which block K+ flux through mitochondrial ATP‐sensitive K+ channels, inhibited the effects of potassium channel openers, without preventing the action of valinomycin. In intact cardiomyocytes, diazoxide also induced mitochondrial depolarization and decreased mitochondrial Ca2+ content. These effects were inhibited by the mitochondrial ATP‐sensitive K+ channel blocker 5‐hydroxydecanoic acid. Thus, potassium channel openers prevent mitochondrial Ca2+ overload by reducing the driving force for Ca2+ uptake and by activating cyclosporin‐sensitive Ca2+ release. In this regard, modulators of an ATP‐sensitive mitochondrial K+ conductance may contribute to the maintenance of mitochondrial Ca2+ homeostasis.

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Section: Resultsmentioning

confidence: 99%

ATP‐sensitive K⁺ channel openers prevent Ca²⁺ overload in rat cardiac mitochondria

Holmuhamedov

Wang

Terzic

1999

The Journal of Physiology

328

218

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“…[34,35] On the other hand, it leads to insufficient intracellular adenosine triphosphate (ATP) supply. [36,37] So, in the case of hypoxia remission, NO is a valuable signaling molecule for plasmons-mediated PDT; [38,39] in the case of poor ATP yield, NO dedicates to plasmons-mediated mild PTT by undermining heat shock proteins (HSPs) synthesis. [40,41] Herein, we fabricate plasmonic dendritic CuPt alloys with highly branched and porous structure, loading with heatsensitive NO donor N, N′-di-sec-butyl-N, N′-dinitroso-1,4phenylenediamine (BNN) (Scheme 1a).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dendritic Plasmonic CuPt Alloys for Closed‐Loop Multimode Cancer Therapy with Remarkably Enhanced Efficacy

Chang

Wang

Liu

et al. 2022

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instruments, laser diagnosis, laser surgery, and so on, motivate the advancement of biomedical domain. [2][3][4] Along with the rapid development of nanotechnology and nanomedicine, the interactions between nanomaterials and lasers led to the emergence of phototherapy. [5][6][7][8] In particular, plasmons that greatly restrict the optical energy into nanometric areas can remarkably strengthen light-matter interactions. [9,10] The localized surface plasmon resonances (LSPR) occur when light-excited electrons oscillate collectively in metallic plasmons, which induces two important effects: highly dense electron clouds near the particle's surface, and strong light absorption at the plasmon resonant frequency. [11,12] As a consequence, plasmonic metals can generate extraordinary photodynamic and photothermal properties. [13,14] Laser-activated plasmons, with spatiotemporal controllability nature, can realize site-targeted tumor phototherapy, effectively avoiding the system toxicity of traditional chemotherapy and radiotherapy. [15,16] With the deepening demands of the translation from basic scientific research to clinical applications, the practical scientific issues in nanomaterials-induced phototherapy, such as therapeutic efficacy and biosafety, have come into focus. [17] In plasmons involved photodynamic therapy (PDT), superoxide anion free radicals (•O 2 − ) are generated The outcome of laser-triggered plasmons-induced phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is significantly limited by the hypoxic tumor microenvironment and the upregulation of heat shock proteins (HSPs) in response to heat stress. Mitochondria, the biological battery of cells, can serve as an important breakthrough to overcome these obstacles. Herein, dendritic triangular pyramidal plasmonic CuPt alloys loaded with heat-sensitive NO donor N, N′-di-sec-butyl-N, N′-dinitroso-1,4phenylenediamine (BNN) is developed. Under 808 nm laser irradiation, plasmonic CuPt can generate superoxide anion free radicals (•O 2 − ) and heat simultaneously. The heat generated can then trigger the release of NO gas, which not only enables gas therapy but also damages the mitochondrial respiratory chain. Impaired mitochondrial respiration leads to reduced oxygen consumption and insufficient intracellular ATP supply, which effectively alleviates tumor hypoxia and undermines the synthesis of HSPs, in turn boosting plasmonic CuPt-based PDT and mild PTT. Additionally, the generated NO and •O 2 − can react to form more cytotoxic peroxynitrite (ONOO − ). This work describes a plasmonic CuPt@BNN (CPB) triggered closed-loop NO gas, free radicals, and mild photothermal therapy strategy that is highly effective at reciprocally promoting antitumor outcomes.

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ATP Synthesis by the Membrane Bound and Isolated H+ ATPases After Jump-Like pH Increase

Blumenfeld

1987

Structure, Dynamics and Function of Biomolecules

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Adenosine Triphosphate Synthesis Coupled to K ⁺ Influx in Mitochondria

Cited by 7 publications

References 27 publications

ATP‐sensitive K⁺ channel openers prevent Ca²⁺ overload in rat cardiac mitochondria

ATP‐sensitive K⁺ channel openers prevent Ca²⁺ overload in rat cardiac mitochondria

Dendritic Plasmonic CuPt Alloys for Closed‐Loop Multimode Cancer Therapy with Remarkably Enhanced Efficacy

ATP Synthesis by the Membrane Bound and Isolated H+ ATPases After Jump-Like pH Increase

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Adenosine Triphosphate Synthesis Coupled to K + Influx in Mitochondria

Cited by 7 publications

References 27 publications

ATP‐sensitive K+ channel openers prevent Ca2+ overload in rat cardiac mitochondria

ATP‐sensitive K+ channel openers prevent Ca2+ overload in rat cardiac mitochondria

Dendritic Plasmonic CuPt Alloys for Closed‐Loop Multimode Cancer Therapy with Remarkably Enhanced Efficacy

ATP Synthesis by the Membrane Bound and Isolated H+ ATPases After Jump-Like pH Increase

Contact Info

Product

Resources

About

Adenosine Triphosphate Synthesis Coupled to K ⁺ Influx in Mitochondria

ATP‐sensitive K⁺ channel openers prevent Ca²⁺ overload in rat cardiac mitochondria

ATP‐sensitive K⁺ channel openers prevent Ca²⁺ overload in rat cardiac mitochondria