Mitochondrial recoupling: a novel therapeutic strategy for cancer?

Baffy, György; Derdák, Zoltán; Robson, Simon C.

doi:10.1038/bjc.2011.245

Cited by 80 publications

(63 citation statements)

References 51 publications

(84 reference statements)

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“…Under pathological conditions, mitochondrial uncoupling has been implicated in tumor growth (1). Some data have shown that cancer cells favor aerobic glycolysis over mitochondrial oxidative phosphorylation to meet rapid and uncontrolled cellular proliferation, although recent data suggest that mitochondrial biogenesis is vital for tumor growth (61).…”

Section: Coronary Collateral Growth: Roles Of Ucps and Ampk Under Normentioning

confidence: 99%

The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth

Pung

Sam

Hardwick

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Coronary collateral growth is a process involving coordination between growth factors expressed in response to ischemia and mechanical forces. Underlying this response is proliferation of vascular smooth muscle and endothelial cells, resulting in an enlargement in the caliber of arterial-arterial anastomoses, i.e., a collateral vessel, sometimes as much as an order of magnitude. An integral element of this cell proliferation is the process known as phenotypic switching in which cells of a particular phenotype, e.g., contractile vascular smooth muscle, must change their phenotype to proliferate. Phenotypic switching requires that protein synthesis occurs and different kinase signaling pathways become activated, necessitating energy to make the switch. Moreover, kinases, using ATP to phosphorylate their targets, have an energy requirement themselves. Mitochondria play a key role in the energy production that enables phenotypic switching, but under conditions where mitochondrial energy production is constrained, e.g., mitochondrial oxidative stress, this switch is impaired. In addition, we discuss the potential importance of uncoupling proteins as modulators of mitochondrial reactive oxygen species production and bioenergetics, as well as the role of AMP kinase as an energy sensor upstream of mammalian target of rapamycin, the master regulator of protein synthesis.angiogenesis; arteriogenesis; redox-dependent signaling; mitochondria THIS ARTICLE is part of a collection on Mitochondria in Cardiovascular Physiology and Disease. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology.org/.

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Section: Coronary Collateral Growth: Roles Of Ucps and Ampk Under Normentioning

confidence: 99%

The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth

Pung

Sam

Hardwick

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…In addition, mitochondrial uncoupling contributes to the dysfunction of wild-type p53 and metabolic reprogramming of cancer cells. Therefore, inhibition of mitochondrial uncoupling by selective inhibitors or some other ways may help restore the functions of p53 to inhibit aerobic glycolysis and provide novel targets for anticancer therapy (70,71).…”

Section: Cytoplasm P53mentioning

confidence: 99%

The Fundamental Role of the p53 Pathway in Tumor Metabolism and Its Implication in Tumor Therapy

Shen

Sun

et al. 2012

Clinical Cancer Research

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It is well established that the altered metabolism exhibited by cancer cells, including high rates of glycolysis, lactate production, and biosynthesis of lipids, nucleotides, and other macromolecules, and which may occur either as a consequence or as a cause of tumorigenesis, plays an essential role in cancer progression. Recently, the tumor suppressor p53 was found to play a central role in this process. Here, we review the role of p53 in modulating tumor metabolism. Specifically, we focus on the functions of p53 in regulating aerobic glycolysis, oxidative phosphorylation, the pentose phosphate pathway, fatty acid synthesis and oxidation, and glutamine metabolism, and we discuss the therapeutic strategy whereby p53 helps to prevent malignant progression.

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“…Upon the trigger of hypoxia, oxygen became not available to act as proton acceptor in the mitochondrial respiration, and the production of ATP would then be greatly impaired. In order to overcome the barrier, cancer cells were found to increase the rate of glycolysis to produce more ATP, which was called Warburg effect (Baffy et al 2011). Metabolism would shift to the formation of lactate in order to recycle back the NAD+ from NADH, leading to the decrease in the pH of the surrounding microenvironment and deterring the surrounding normal cells to grow (Baffy et al 2011).…”

Section: Relationship Between Electric Current With Ros and Mmpmentioning

confidence: 99%

“…Previous studies had reported the re-engineering of cellular metabolism in cancer cells (Baffy et al 2011), which might improve the survival of cancer cells in adverse environment, e.g., hypoxia. Upon the trigger of hypoxia, oxygen became not available to act as proton acceptor in the mitochondrial respiration, and the production of ATP would then be greatly impaired.…”

Section: Relationship Between Electric Current With Ros and Mmpmentioning

confidence: 99%

UCP2- and non-UCP2-mediated electric current in eukaryotic cells exhibits different properties

Wang

MoYung

Zhang

et al. 2015

Environ Sci Pollut Res

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Using live eukaryotic cells, including cancer cells, MCF-7 and HCT-116, normal hepatocytes and red blood cells in anode and potassium ferricyanide in cathode of MFC could generate bio-based electric current. Electrons and protons generated from the metabolic reaction in both cytosol and mitochondria contributing to the leaking would mediate the generation of electric current. Both resveratrol (RVT) and 2,4-dinitrophenol (DNP) used to induce proton leak in mitochondria were found to promote electric current production in all cells except red blood cells without mitochondria. Proton leak might be important for electric current production by bringing the charge balance in cells to enhance the further electron leak. The induced electric current by RVT can be blocked by Genipin, an inhibitor of UCP2-mediated proton leak, while that induced by DNP cannot. RVT could reduce reactive oxygen species (ROS) level in cells better than that of DNP. In addition, RVT increased mitochondrial membrane potential (MMP), while DNP decreased it. Results highly suggested the existence of at least two types of electric current that showed different properties. They included UCP2-mediated and non-UCP2-mediated electric current. UCP2-mediated electric current exhibited higher reactive oxygen species (ROS) reduction effect per unit electric current production than that of non-UCP2-mediated electric current. Higher UCP2-mediated electric current observed in cancer cells might contribute to the mechanism of drug resistence. Correlation could not be established between electric current production with either ROS and MMP without distinguishing the types of electric current.

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Mitochondrial recoupling: a novel therapeutic strategy for cancer?

Cited by 80 publications

References 51 publications

The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth

The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth

The Fundamental Role of the p53 Pathway in Tumor Metabolism and Its Implication in Tumor Therapy

UCP2- and non-UCP2-mediated electric current in eukaryotic cells exhibits different properties

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