Targeting mitochondrial cardiolipin and the cytochrome <i>c</i>/cardiolipin complex to promote electron transport and optimize mitochondrial <scp>ATP</scp> synthesis

Birk, Alexander; Chao, Wesley; Bracken, Clay; Warren, Joel; Szeto, Hazel H.

doi:10.1111/bph.12468

Cited by 246 publications

(266 citation statements)

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“…In summary, mitochondria are a major source of ROS and RNS, species that can regulate mitochondrial activity through different mechanisms, including modulation of O 2 consumption and OXPHOS, induction of mitochondrial membrane permeability transition, regulation of mitochondrial biogenesis, mitochondrial dynamics, and autophagy/mitophagy (23,28,218,238). Another field of action involves the presence of oxidative stress and its consequences, such as lipid peroxidation, protein and DNA oxidation, which occur when there is a strong disruption of the cellular redox homeostasis (Fig.…”

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confidence: 99%

“…The mechanism proposed for this action of SS-31 is its selective binding to cardiolipin and inhibition of cardiolipin peroxidation by cytochrome c peroxidase activity. Actually, a recent report has explored in detail the interaction of SS-31 and cardiolipin (23). Using as a model liposomes and bicelles containing phosphatidylcholine alone or with cardiolipin, Birk et al (23) proved that SS-31 selectively targeted cardiolipin and that this interaction occured only with liposomes and bicelles containing cardiolipin in a ratio of 1:1.…”

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confidence: 99%

“…Actually, a recent report has explored in detail the interaction of SS-31 and cardiolipin (23). Using as a model liposomes and bicelles containing phosphatidylcholine alone or with cardiolipin, Birk et al (23) proved that SS-31 selectively targeted cardiolipin and that this interaction occured only with liposomes and bicelles containing cardiolipin in a ratio of 1:1. Moreover, SS-31 modulated the interaction of cardiolipin with cytochrome c, inhibiting cytochrome c/cardiolipin complex peroxidase activity while protecting the ability of cyttochrome c to serve as an electron carrier.…”

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confidence: 99%

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Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

Apostolova

Víctor

2015

Antioxidants & Redox Signaling

222

147

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Mitochondrial function and specifically its implication in cellular redox/oxidative balance is fundamental in controlling the life and death of cells, and has been implicated in a wide range of human pathologies. In this context, mitochondrial therapeutics, particularly those involving mitochondria-targeted antioxidants, have attracted increasing interest as potentially effective therapies for several human diseases. For the past 10 years, great progress has been made in the development and functional testing of molecules that specifically target mitochondria, and there has been special focus on compounds with antioxidant properties. In this review, we will discuss several such strategies, including molecules conjugated with lipophilic cations (e.g., triphenylphosphonium) or rhodamine, conjugates of plant alkaloids, amino-acid-and peptide-based compounds, and liposomes. This area has several major challenges that need to be confronted. Apart from antioxidants and other redox active molecules, current research aims at developing compounds that are capable of modulating other mitochondria-controlled processes, such as apoptosis and autophagy. Multiple chemically different molecular strategies have been developed as delivery tools that offer broad opportunities for mitochondrial manipulation. Additional studies, and particularly in vivo approaches under physiologically relevant conditions, are necessary to confirm the clinical usefulness of these molecules. Antioxid. Redox Signal. 22, 686-729.

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Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

Apostolova

Víctor

2015

Antioxidants & Redox Signaling

222

147

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“…low P/O) and some damage that may be treatable (e.g. cardiolipin oxidation; Birk et al, 2014;Szeto, 2014) to at least partially restore function of mitochondria to improve exercise function of old animals, including elderly humans.…”

Section: Identifying Mechanismsmentioning

confidence: 99%

“…This greater rise in ATP max than in P/O implies not only improvement in mitochondrial coupling efficiency but also a rapid rise in the capacity for electron transport chain (ETC) flux (O 2 uptake capacity). The mechanism for this increase in the ETC flux capacity is thought to be stabilization of cardiolipin on the inner mitochondrial membrane, thereby restoring a key bridge in electron flow through the ETC (Birk et al, 2014;Szeto, 2014). These treatments demonstrate that there are many sites in oxidative phosphorylation that are potential targets for treatment to improve mitochondrial function.…”

Section: Introductionmentioning

confidence: 99%

Mitochondria to motion: optimizing oxidative phosphorylation to improve exercise performance

Conley

2016

Journal of Experimental Biology

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Mitochondria oxidize substrates to generate the ATP that fuels muscle contraction and locomotion. This review focuses on three steps in oxidative phosphorylation that have independent roles in setting the overall mitochondrial ATP flux and thereby have direct impact on locomotion. The first is the electron transport chain, which sets the pace for oxidation. New studies indicate that the electron transport chain capacity per mitochondria declines with age and disease, but can be revived by both acute and chronic treatments. The resulting higher ATP production is reflected in improved muscle power output and locomotory performance. The second step is the coupling of ATP supply from O 2 uptake (mitochondrial coupling efficiency). Treatments that elevate mitochondrial coupling raise both exercise efficiency and the capacity for sustained exercise in both young and old muscle. The final step is ATP synthesis itself, which is under dynamic control at multiple sites to provide the 50-fold range of ATP flux between resting muscle and exercise at the mitochondrial capacity. Thus, malleability at sites in these subsystems of oxidative phosphorylation has an impact on ATP flux, with direct effects on exercise performance. Interventions are emerging that target these three independent subsystems to provide many paths to improve ATP flux and elevate the muscle performance lost to inactivity, age or disease.

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Precise Subcellular Organelle Targeting for Boosting Endogenous‐Stimuli‐Mediated Tumor Therapy

Zhen

Wang

et al. 2021

Advanced Materials

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to their noninvasive and specific treatment modality from selective irradiation. [1b] However, external energy, such as light, ionizing radiation or ultrasound, is required in these therapies, which obstructs their further development due to the limited penetration depth of the laser, safety concerns of radiation, therapeutic resistance and spatio-temporal constraints of some specific equipments. In-depth exploiting the differences between the tumor microenvironment (TME) and normal organs provides an alternative way that without specific devices. Take full advantage of the TME, endogenousstimuli-mediated therapy is a novel concept in tumor treatment.The TME, mainly composed of tumor cells, vessels, lymphatic vessels, immune cells, fibroblasts, and extracellular matrix (ECM), [4] which provides a suitable environment for survival, division, angiogenesis, and metastasis of tumor cells. During the growth of tumor tissue, some regions are hypoxic [5] due to abnormal vascularization and inferior blood accommodation. [6] Normal cells can decompose glucose into pyruvate through glycolysis in the cytoplasm under normoxic conditions and the generated pyruvate is transported to the mitochondria and further decomposed into carbon dioxide, [7] which is known as tricarboxylic acid cycle (TCA). In hypoxic tumor tissues, the TCA pathway is restricted due to the insufficiency of oxygen supply. Instead, pyruvate is reduced to lactic acid to produce energy with much lower efficiency. This process on the one hand increases the consumption of glucose and pyruvate, and on the other hand increases acidity of the extracellular TME (pH value: 6.5-6.8) due to the secreted lactic acid. [8] Another noteworthy property of the TME is the increased level of reactive oxygen species (ROS). [9] The term ROS mainly includes hydrogen peroxide (H 2 O 2 ), singlet oxygen ( 1 O 2 ), hydroxyl radical (•OH), superoxide (•O 2 − ), ozone, lipid peroxides, hypochlorous acid, which often determines many biological responses and metabolic processes within the tumor [10] directly and/or indirectly. [11] Increased expression of ROS-scavenging enzymes and antioxidant molecules could balance the high levels of ROS, which may contribute to the accommodative response of tumor cells to many therapies. [12] For example, glutathione (GSH) plays a vital role in the protection of cells against lectrophilic and oxidative stress as it is engaged in the metabolism and detoxification process of many cytotoxic and carcinogenic species with the oxidation of GSH to its oxidized Though numerous external-stimuli-triggered tumor therapies, including phototherapy, radiotherapy, and sonodynamic therapy have made great progress in cancer therapy, the low penetration depth of the laser, safety concerns of radiation, the therapeutic resistance, and the spatio-temporal constraints of the specific equipment restrict their convenient clinical applications. What is more, the inherent physiological barriers of the tumor microenvironment (TME), including hypoxia, heterogeneity, and...

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Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis

Cited by 246 publications

References 55 publications

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

Mitochondria to motion: optimizing oxidative phosphorylation to improve exercise performance

Precise Subcellular Organelle Targeting for Boosting Endogenous‐Stimuli‐Mediated Tumor Therapy

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