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Imaging mitochondrial redox potential and its possible link to tumor metastatic potential

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Abstract

Cellular redox states can regulate cell metabolism, growth, differentiation, motility, apoptosis, signaling pathways, and gene expressions etc. A growing body of literature suggest the importance of redox status for cancer progression. While most studies on redox state were done on cells and tissue lysates, it is important to understand the role of redox state in a tissue in vivo/ex vivo and image its heterogeneity. Redox scanning is a clinical-translatable method for imaging tissue mitochondrial redox potential with a submillimeter resolution. Redox scanning data in mouse models of human cancers demonstrate a correlation between mitochondrial redox state and tumor metastatic potential. I will discuss the significance of this correlation and possible directions for future research.

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References

  • Adler V, Yin ZM, Tew KD, Ronai Z (1999) Role of redox potential and reactive oxygen species in stress signaling. Oncogene 18(45):6104–6111

    Article  CAS  Google Scholar 

  • Agarwal AK, Auchus RJ (2005) Minireview: cellular redox state regulates hydroxysteroid dehydrogenase activity and intracellular hormone potency. Endocrinology 146(6):2531–2538

    Article  CAS  Google Scholar 

  • Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, Thomas-Tikhonenko A, Thompson CB (2007) Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest 117(2):326–336

    Article  CAS  Google Scholar 

  • Banerjee R (2008) Redox biochemistry. John Wiley & Sons, Hoboken

    Google Scholar 

  • Barlow CH, Harden WR 3rd, Harken AH, Simson MB, Haselgrove JC, Chance B, O’Connor M, Austin G (1979) Fluorescence mapping of mitochrondrial redox changes in heart and brain. Crit Care Med 7(9):402–406

    Article  CAS  Google Scholar 

  • Becker DF, Zhu W, Moxley MA (2011) Flavin redox switching of protein functions. Antioxid Redox Signal 14(6):1079–1091

    Article  CAS  Google Scholar 

  • Blinova K, Levine RL, Boja ES, Griffiths GL, Shi ZD, Ruddy B, Balaban RS (2008) Mitochondrial NADH fluorescence is enhanced by Complex I binding. Biochemistry 47(36):9636–9645

    Article  CAS  Google Scholar 

  • Bohndiek SE, Kettunen MI, Hu D-e, Kennedy BWC, Boren J, Gallagher FA, Brindle KM (2011) Hyperpolarized [1-13C]-ascorbic and dehydroascorbic acid: vitamin C as a probe for imaging redox status in vivo. J Am Chem Soc 133(30):11795–11801

    Google Scholar 

  • Brown JQ, Wilke LG, Geradts J, Kennedy SA, Palmer GM, Ramanujam N (2009) Quantitative optical spectroscopy: a robust tool for direct measurement of breast cancer vascular oxygenation and total hemoglobin content in vivo. Cancer Res 69(7):2919–2926

    Article  CAS  Google Scholar 

  • Cai K, Xu HN, Singh A, Haris M, Reddy R, Li LZ (2012). Characterizing prostate tumor mouse xenografts with CEST & MT MRI and redox scanning. Adv Exp Med Biol

  • Cairns RA, Harris IS, Mak TW (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11(2):85–95. doi:10.1038/nrc2981

    Article  CAS  Google Scholar 

  • Chance B (1966) Spectrophotometric and kinetic studies of flavoproteins in tissues, cell suspensions, mitochondria and their fragments. In: Slater EC (ed) Flavins and flavoproteins. Elsevier, Amsterdam, pp 498–510

    Google Scholar 

  • Chance B, Baltscheffsky H (1958) Respiratory enzymes in oxidative phosphorylation. 7. Binding of intramitochondrial reduced pyridine nucleotide. J Biol Chem 233(3):736–739

    CAS  Google Scholar 

  • Chance B, Cohen P, Jobsis F, Schoener B (1962) Intracellular oxidation-reduction states in vivo. Science 137:499–508

    Article  CAS  Google Scholar 

  • Chance B, Jobsis F (1959) Changes in fluorescence in a frog sartorius muscle following a twitch. Nature 184(4681):195–196

    Article  CAS  Google Scholar 

  • Chance B, Schoener B (1966) Fluorometric studies of flavin component of the respiratory chain. In: Slater EC (ed) Flavins and flavoproteins. Elsevier, Amsterdam, pp 510–519

    Google Scholar 

  • Chance B, Schoener B, Oshino R, Itshak F, Nakase Y (1979) Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals. J Biol Chem 254(11):4764–4771

    CAS  Google Scholar 

  • Chance B, Williams GR (1955a) A method for the localization of sites for oxidative phosphorylation. Nature 176(4475):250–254

    Article  CAS  Google Scholar 

  • Chance B, Williams GR (1955b) Respiratory enzymes in oxidative phosphorylation. III. The steady state. J Biol Chem 217(1):409–428

    CAS  Google Scholar 

  • Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC (2008) The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452(7184):230–233. doi:10.1038/nature06734

    Article  CAS  Google Scholar 

  • Chung Y, Jue T (1992) 1H NMR observation of redox potential in liver. Biochemistry 31(45):11159–11165

    Article  CAS  Google Scholar 

  • Cook JA, Gius D, Wink DA, Krishna MC, Russo A, Mitchell JB (2004) Oxidative stress, redox, and the tumor microenvironment. Semin Radiat Oncol 14(3):259–266

    Article  Google Scholar 

  • Dang CV (1999) c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol 19:1–11

    CAS  Google Scholar 

  • Dooley CT, Dore TM, Hanson GT, Jackson WC, Remington SJ, Tsien RY (2004) Imaging dynamic redox changes in mammalian cells with green fluorescent protein indicators. J Biol Chem 279(21):22284–22293

    Article  CAS  Google Scholar 

  • Dorward A, Sweet S, Moorehead R, Singh G (1997) Mitochondrial contributions to cancer cell physiology: redox balance, cell cycle, and drug resistance. J Bioenerg Biomembr 29(4):385–392

    Article  CAS  Google Scholar 

  • Drezek R, Brookner C, Pavlova I, Boiko I, Malpica A, Lotan R, Follen M, Richards-Kortum R (2001) Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia. Photochem Photobiol 73(6):636–641

    Article  CAS  Google Scholar 

  • Fidler IJ, Hart IR (1982) Biological diversity in metastatic neoplasms - origins and implications. Science 217(4564):998–1003

    Article  CAS  Google Scholar 

  • Fidler IJ, Kripke ML (1977) Metastasis results from preexisting variant cells within a malignant-tumor. Science 197(4306):893–895

    Article  CAS  Google Scholar 

  • Fisher AB, Furia L, Chance B (1976) Evaluation of redox state of isolated perfused rat lung. Am J Physiol 230(5):1198–1204

    CAS  Google Scholar 

  • Gaustad JV, Benjaminsen IC, Graff BA, Brurberg KG, Ruud EBM, Rofstad EK (2005) Intratumor heterogeneity in blood perfusion in orthotopic human melanoma xenografts assessed by dynamic contrast-enhanced magnetic resonance imaging. J Magn Reson Imaging 21(6):792–800

    Article  Google Scholar 

  • Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366(10):883–892

    Article  CAS  Google Scholar 

  • Gough NR (2009) Focus issue: the long and short of redox signaling. Sci Signal 2(90):eg12

    Article  Google Scholar 

  • Grek CL, Tew KD (2010) Redox metabolism and malignancy. Curr Opin Pharmacol 10(4):362–368

    Article  CAS  Google Scholar 

  • Gu Y, Qian Z, Chen J, Blessington D, Ramanujam N, Chance B (2002) High-resolution three-dimensional scanning optical image system for intrinsic and extrinsic contrast agents in tissue. Rev Sci Instrum 73(1):172–178

    Article  CAS  Google Scholar 

  • Gutscher M, Pauleau AL, Marty L, Brach T, Wabnitz GH, Samstag Y, Meyer AJ, Dick TP (2008) Real-time imaging of the intracellular glutathione redox potential. Nature Methods 5(6):553–559

    Article  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

    Article  CAS  Google Scholar 

  • Haselgrove JC, Bashford CL, Barlow CH, Quistorff B, Chance B, Mayevsky A (1990) Time resolved 3-dimensional recording of redox ratio during spreading depression in gerbil brain. Brain Res 506(1):109–114

    Article  CAS  Google Scholar 

  • Hassinen I, Chance B (1968) Oxidation-reduction properties of the mitochondrial flavoprotein chain. Biochem Biophys Res Commun 31(6):895–900

    Article  CAS  Google Scholar 

  • Hsu PP, Sabatini DM (2008) Cancer cell metabolism: Warburg and beyond. Cell 134(5):703–707

    Article  CAS  Google Scholar 

  • Hung Yin P, Albeck John G, Tantama M, Yellen G (2011) Imaging cytosolic NADH-NAD+ redox state with a genetically encoded fluorescent biosensor. Cell Metabolism 14(4):545–554

    Article  CAS  Google Scholar 

  • Hyodo F, Matsumoto K, Matsumoto A, Mitchell JB, Krishna MC (2006) Probing the intracellular redox status of tumors with magnetic resonance imaging and redox-sensitive contrast agents. Cancer Res 66(20):9921–9928

    Article  CAS  Google Scholar 

  • Hyodo F, Murugesan R, Matsumoto K, Hyodo E, Subramanian S, Mitchell JB, Krishna MC (2008) Monitoring redox-sensitive paramagnetic contrast agent by EPRI, OMRI and MRI. J Magn Reson 190(1):105–112

    Article  CAS  Google Scholar 

  • Ido Y (2007) Pyridine nucleotide redox abnormalities in diabetes. Antioxid Redox Signal 9(7):931–942

    Article  CAS  Google Scholar 

  • Ishikawa K, Koshikawa N, Takenaga K, Nakada K, Hayashi JI (2008a) Reversible regulation of metastasis by ROS-generating mtDNA mutations. Mitochondrion 8(4):339–344

    Article  CAS  Google Scholar 

  • Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H, Nakada K, Honma Y, Hayashi J (2008b) ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science 320(5876):661–664

    Article  CAS  Google Scholar 

  • Ishimoto T, Nagano O, Yae T, Tamada M, Motohara T, Oshima H, Oshima M, Ikeda T, Asaba R, Yagi H, Masuko T, Shimizu T, Ishikawa T, Kai K, Takahashi E, Imamura Y, Baba Y, Ohmura M, Suematsu M, Baba H, Saya H (2011) CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc and thereby promotes tumor growth. Cancer Cell 19(3):387–400

    Article  CAS  Google Scholar 

  • Kaelin WG, Thompson CB (2010) Q&A: cancer: clues from cell metabolism. Nature 465(7298):562–564

    Article  CAS  Google Scholar 

  • Keshari KR, Kurhanewicz J, Bok R, Larson PEZ, Vigneron DB, Wilson DM (2011) Hyperpolarized (13)C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging. Proc Natl Acad Sci U S A 108(46):18606–18611

    Article  CAS  Google Scholar 

  • King A, Selak MA, Gottlieb E (2006) Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene 25(34):4675–4682

    Article  CAS  Google Scholar 

  • Kitai T, Tanaka A, Tokuka A, Ozawa K, Iwata S, Chance B (1992) Changes in the redox distribution of rat liver by ischemia. Anal Biochem 206(1):131–136

    Article  CAS  Google Scholar 

  • Koppenol WH, Bounds PL, Dang CV (2011) Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer 11(5):325–337. doi:10.1038/nrc3038

    Article  CAS  Google Scholar 

  • Lehninger AL, Nelson DL, Cox MM (1993) Principles of biochemistry, 2nd edn. Worth Publishers, New York

    Google Scholar 

  • Lemasters JJ, Nieminen AL (2001) Mitochondria in pathogenesis. Kluwer Academic/Plenum Publishers, New York

    Google Scholar 

  • Levitt JM, McLaughlin-Drubin ME, Munger K, Georgakoudi I (2011) Automated biochemical, morphological, and organizational assessment of precancerous changes from endogenous two-photon fluorescence images. PLoS One 6(9)

  • Li LZ, Xu HN, Ranji M, Nioka S, Chance B (2009a) Mitochondrial redox imaging for cancer diagnostic and therapeutic studies. Journal of Innovative Optical Health Sciences 2:325–341

    Article  Google Scholar 

  • Li LZ, Zhou R, Xu HN, Moon L, Zhong TX, Kim EJ, Qiao H, Reddy R, Leeper D, Chance B, Glickson JD (2009b) Quantitative magnetic resonance and optical imaging biomarkers of melanoma metastatic potential. Proc Natl Acad Sci U S A 106(16):6608–6613

    Article  CAS  Google Scholar 

  • Li LZJ, Zhou R, Zhong TX, Moon L, Kim EJ, Qiao H, Pickup S, Hendrix MJ, Leeper D, Chance B, Glickson JD (2007) Predicting melanoma metastatic potential by optical and magnetic resonance imaging. In: Maguire DJ, Bruley DF, Harrison DK (eds) Oxygen transport to tissue Xxviii (Vol. 599, Advances in Experimental Medicine and Biology). Springer, Berlin, pp 67–78

    Chapter  Google Scholar 

  • Lisanti MP, Martinez-Outschoorn UE, Lin Z, Pavlides S, Whitaker-Menezes D, Pestell RG, Howell A, Sotgia F (2011) Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis The seed and soil also needs “fertilizer”. Cell Cycle 10(15):2440–2449

    Article  CAS  Google Scholar 

  • Liu Q, Grant G, Li JJ, Zhang Y, Hu FY, Li SQ, Wilson C, Chen K, Bigner D, Tuan VD (2011) Compact point-detection fluorescence spectroscopy system for quantifying intrinsic fluorescence redox ratio in brain cancer diagnostics. J Biomed Opt 16(3)

  • Locasale Jason W, Cantley Lewis C (2011) Metabolic flux and the regulation of mammalian cell growth. Cell Metabolism 14(4):443–451

    Article  CAS  Google Scholar 

  • Lum JJ, Bauer DE, Kong M, Harris MH, Li C, Lindsten T, Thompson CB (2005) Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 120(2):237–248

    Article  CAS  Google Scholar 

  • Ma X-H, Piao S, Wang D, McAfee QW, Nathanson KL, Lum JJ, *Li LZ, *Amaravadi RK (Equal contribution) (2011) Measurements of tumor cell autophagy predict invasiveness, resistance to chemotherapy, and survival in melanoma. Clin Canc Res 17(10):3478–3489

    Google Scholar 

  • Mac Manus M, Hicks RJ (2008) The use of positron emission tomography (PET) in the staging/evaluation, treatment, and follow-up of patients with lung cancer: a critical review. Int J Radiat Oncol Biol Phys 72(5):1298–1306

    Article  Google Scholar 

  • Maccarrone M, Brune B (2009) Redox regulation in acute and chronic inflammation. Cell Death Differ 16(8):1184–1186

    Article  CAS  Google Scholar 

  • Masters BR, Falk S, Chance B (1981) In vivo flavoprotein redox measurements of rabbit corneal normoxic-anoxic transitions. Curr Eye Res 1(10):623–627

    Article  Google Scholar 

  • Matsumoto K, Hyodo F, Matsumoto A, Koretsky AP, Sowers AL, Mitchell JB, Krishna MC (2006) High-resolution mapping of tumor redox status by magnetic resonance imaging using nitroxides as redox-sensitive contrast agents. Clin Cancer Res 12(8):2455–2462

    Article  CAS  Google Scholar 

  • Mayevsky A (2009) Mitochondrial function and energy metabolism in cancer cells: past overview and future perspectives. Mitochondrion 9(3):165–179

    Article  CAS  Google Scholar 

  • Mayevsky A, Rogatsky GG (2007) Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies. Am J Physiol Cell Physiol 292(2):C615–640

    Article  CAS  Google Scholar 

  • Mayevsky A, Zarchin N, Kaplan H, Haveri J, Haselgroove J, Chance B (1983) Brain metabolic responses to ischemia in the mongolian gerbil: in vivo and freeze trapped redox scanning. Brain Res 276(1):95–107

    Article  CAS  Google Scholar 

  • Modica-Napolitano JS, Kulawiec M, Singh KK (2007) Mitochondria and human cancer. Curr Mol Med 7(1):121–131

    Article  CAS  Google Scholar 

  • Mueller-Klieser W, Kroeger M, Walenta S, Rofstad EK (1991) Comparative imaging of structure and metabolites in tumors. Int J Radiat Biol 60(1–2):147–159

    Article  CAS  Google Scholar 

  • Mueller-Klieser W, Walenta S (1993) Geographical mapping of metabolites in biological tissue with quantitative bioluminescence and single photon imaging. Histochem J 25(6):407–420

    Article  CAS  Google Scholar 

  • Nichols MG, Barth EE, Nichols JA (2005) Reduction in DNA synthesis during two-photon microscopy of intrinsic reduced nicotinamide adenine dinucleotide fluorescence. Photochem Photobiol 81(2):259–269

    Article  CAS  Google Scholar 

  • Nkabyo YS, Ziegler TR, Gu LH, Watson WH, Jones DP (2002) Glutathione and thioredoxin redox during differentiation in human colon epithelial (Caco-2) cells. Am J Physiol Gastrointest Liver Physiol 283(6):G1352–G1359

    CAS  Google Scholar 

  • Nowell PC (1976) Clonal evolution of tumor-cell populations. Science 194(4260):23–28

    Article  CAS  Google Scholar 

  • Olovnikov IA, Kravchenko JE, Chumakova PM (2009) Homeostatic functions of the p53 tumor suppressor: regulation of energy metabolism and antioxidant defense. Semin Canc Biol 19(1):32–41

    Article  CAS  Google Scholar 

  • Olschewski A, Hong ZG, Peterson DA, Nelson DP, Porter VA, Weir EK (2004) Opposite effects of redox status on membrane potential, cytosolic calcium, and tone in pulmonary arteries and ductus arteriosus. Am J Physiol Lung Cell Mol Physiol 286(1):L15–L22

    Article  CAS  Google Scholar 

  • Orrenius S, Gogvadze A, Zhivotovsky B (2007) Mitochondrial oxidative stress: implications for cell death. Annu Rev Pharmacol Toxicol 47:143–183

    Article  CAS  Google Scholar 

  • Ozawa K, Chance B, Tanaka A, Iwata S, Kitai T, Ikai I (1992) Linear correlation between acetoacetate beta-hydroxybutyrate in arterial blood and oxidized flavoprotein reduced pyridine-nucleotide in freeze-trapped human liver-tissue. Biochimica Et Biophysica Acta 1138(4):350–352

    Article  CAS  Google Scholar 

  • Pani G, Galeotti T, Chiarugi P (2010) Metastasis: cancer cell’s escape from oxidative stress. Cancer Metastasis Rev 29:351–378

    Article  CAS  Google Scholar 

  • Pani G, Giannoni E, Galeotti T, Chiarugi P (2009) Redox-based escape mechanism from death: the cancer lesson. Antioxidants & Redox Signaling 11:2791–2806

    Article  CAS  Google Scholar 

  • Pedersen PL (2007) Warburg, me and hexokinase 2: multiple discoveries of key molecular events underlying one of cancers’ most common phenotypes, the “Warburg Effect”, i.e., elevated glycolysis in the presence of oxygen. J Bioenerg Biomembr 39(3):211–222

    Article  CAS  Google Scholar 

  • Pelicano H, Lu W, Zhou Y, Zhang W, Chen Z, Hu Y, Huang P (2009) Mitochondrial dysfunction and reactive oxygen species imbalance promote breast cancer cell motility through a CXCL14-mediated mechanism. Cancer Res 69(6):2375–2383

    Article  CAS  Google Scholar 

  • Puppi A, Dely M (1983) Tissue redox-state potential (E0) – As regulator of physiological processes. Acta Biologica Hungarica 34:323–350

    CAS  Google Scholar 

  • Quistorff B, Haselgrove JC, Chance B (1985) High resolution readout of 3-D metabolic organ structure: an automated, low-temperature redox ratio-scanning instrument. Anal Biochem 148:389–400

    Article  CAS  Google Scholar 

  • Quon A, Gambhir SS (2005) FDG-PET and beyond: molecular breast cancer imaging. J Clin Oncol 23(8):1664–1673

    Article  CAS  Google Scholar 

  • Ramanujam N, Richards-Kortum R, Thomsen S, Mahadevan-Jansen A, Follen M, Chance B (2001) Low temperature fluorescence imaging of freeze-trapped human cervical tissues. Opt Express 8(6):335–343

    Article  CAS  Google Scholar 

  • Ramanujan VK, Zhang JH, Biener E, Herman B (2005) Multiphoton fluorescence lifetime contrast in deep tissue imaging: prospects in redox imaging and disease diagnosis. J Biomed Opt 10(5)

  • Ranji M, Nioka S, Xu N, Wu B, Li LZ, Jaggard DL, Chance B (2009) Fluorescent images of mitochondrial redox states in in situ mouse hypoxic ischemic intestines. Journal of International Optical Health Sciences 2:365–374

    Article  Google Scholar 

  • Rocheleau JV, Head WS, Piston DW (2004) Quantitative NAD(P)H/flavoprotein autofluorescence imaging reveals metabolic mechanisms of pancreatic islet pyruvate response. J Biol Chem 279(30):31780–31787

    Article  CAS  Google Scholar 

  • Sarsour EH, Kumar MG, Chaudhuri L, Kalen AL, Goswami PC (2009) Redox control of the cell cycle in health and disease. Antioxid Redox Signal 11:2985–3011

    Article  CAS  Google Scholar 

  • Sato B, Tanaka A, Mori S, Yanabu N, Kitai T, Tokuka A, Inomoto T, Iwata S, Yamaoka Y, Chance B (1995) Quantitative analysis of redox gradient within the rat liver acini by fluorescence images: effects of glucagon perfusion. Biochim Biophys Acta 1268(1):20–26

    Article  Google Scholar 

  • Sattlar UGA, Walenta S, Mueller-Klieser W (2007) A bioluminescence technique for quantitative and structure-associated imaging of pyruvate. Lab Investig 87(1):84–92

    Article  CAS  Google Scholar 

  • Sattler UGA, Walenta S, Mueller-Klieser W (2007) Lactate and redox status in malignant tumors. Anaesthesist 56(5):466–469

    Article  CAS  Google Scholar 

  • Scholz R, Thurman RG, Williamson JR, Chance B, Bucher T (1969) Flavin and pyridine nucleotide oxidation-reduction changes in perfused rat liver. I. Anoxia and subcellular localization of fluorescent flavoproteins. J Biol Chem 244(9):2317–2324

    CAS  Google Scholar 

  • Schroeder T, Yuan H, Viglianti BL, Peltz C, Asopa S, Vujaskovic Z, Dewhirst MW (2005) Spatial heterogeneity and oxygen dependence of glucose consumption in R3230Ac and fibrosarcomas of the Fischer 344 rat. Cancer Res 65(12):5163–5171

    Article  CAS  Google Scholar 

  • Semenza GL (2010) HIF-1: upstream and downstream of cancer metabolism. Curr Opin Genet Dev 20(1):51–56

    Article  CAS  Google Scholar 

  • Senda T, Senda M, Kimura S, Ishida T (2009) Redox control of protein conformation in flavoproteins. Antioxid Redox Signal 11(7):1741–1766

    Article  CAS  Google Scholar 

  • Shah SP, Roth A, Goya R, Oloumi A, Ha G, Zhao Y, Turashvili G, Ding J, Tse K, Haffari G, Bashashati A, Prentice LM, Khattra J, Burleigh A, Yap D, Bernard V, McPherson A, Shumansky K, Crisan A, Giuliany R, Heravi-Moussavi A, Rosner J, Lai D, Birol I, Varhol R, Tam A, Dhalla N, Zeng T, Ma K, Chan SK, Griffith M, Moradian A, Cheng SWG, Morin GB, Watson P, Gelmon K, Chia S, Chin S-F, Curtis C, Rueda OM, Pharoah PD, Damaraju S, Mackey J, Hoon K, Harkins T, Tadigotla V, Sigaroudinia M, Gascard P, Tlsty T, Costello JF, Meyer IM, Eaves CJ, Wasserman WW, Jones S, Huntsman D, Hirst M, Caldas C, Marra MA, Aparicio S (2012) The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature, advance online publication. doi:10.1038/nature10933

  • Shiino A, Haida M, Beauvoit B, Chance B (1999) Three-dimensional redox image of the normal gerbil brain. Neuroscience 91(4):1581–1585

    Article  CAS  Google Scholar 

  • Skala MC, Riching KM, Gendron-Fitzpatrick A, Eickhoff J, Eliceiri KW, White JG, Ramanujam N (2007a) In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia. [Research Support, N.I.H., Extramural Research Support, U.S. Gov’t, Non-P.H.S.]. Proc Natl Acad Sci U S A 104(49):19494–19499

    Article  CAS  Google Scholar 

  • Skala MC, Riching KM, Gendron-Fitzpatrick A, Eickhoff J, Eliceiri KW, White JG, Ramanujam N (2007b) In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia. Proc Natl Acad Sci U S A 104(49):19494–19499

    Article  CAS  Google Scholar 

  • Tachtsidis I, Tisdall MM, Pritchard C, Leung TS, Ghosh A, Elwell CE, Smith M (2011) Analysis of the changes in the oxidation of brain tissue cytochrome-c-oxidase in traumatic brain injury patients during hypercapnoea a broadband NIRS study. In: LaManna JC, Puchowicz MA, Xu K, Harrison DK, Bruley DF (eds) Oxygen transport to tissue Xxxii (Vol. 701, Advances in Experimental Medicine and Biology). Springer, Berlin, pp 9–14

    Google Scholar 

  • Taylor BL, Rebbapragada A, Johnson MS (2001) The FAD-PAS domain as a sensor for behavioral responses in escherichia coli. Antioxid Redox Signal 3(5):867–879

    Article  CAS  Google Scholar 

  • Thompson CB (2009) Metabolic enzymes as oncogenes or tumor suppressors. N Engl J Med 360(8):813–815

    Article  CAS  Google Scholar 

  • Tisdall MM, Tachtsidis I, Leung TS, Elwell CE, Smith M (2007) Near-infrared spectroscopic quantification of changes in the concentration of oxidized cytochrome c oxidase in the healthy human brain during hypoxemia. J Biomed Opt 12(2)

  • Veech RL (2006) The determination of the redox states and phosphorylation potential in living tissues and their relationship to metabolic control of disease phenotypes. Biochem Mol Biol Educ 34(3):168–179

    Article  CAS  Google Scholar 

  • Weir EK, Hong ZG, Porter VA, Reeve HL (2002) Redox signaling in oxygen sensing by vessels. Respir Physiol Neurobiol 132(1):121–130

    Article  CAS  Google Scholar 

  • Xu HN, Addis RC, Goings DF, Nioka S, Chance B, Gearhart JD, Li LZ (2011a) Imaging redox state heterogeneity within individual embryonic stem cell colonies. Journal of Innovative Optical Health Sciences 4:279–288

    Article  Google Scholar 

  • Xu HN, Nioka S, Chance B, Li LZ (2011b) Heterogeneity of mitochondrial redox state in premalignant pancreas in a PTEN null transgenic mouse model. Adv Exp Med Biol 701:207–213

    Article  CAS  Google Scholar 

  • Xu HN, Nioka S, Chance B, Zheng G, Li LZ (2011c) High-resolution simultaneous mapping of mitochondrial redox state and glucose uptake in human breast tumor xenografts. In: Advances in experimental medicine and biology (Vol. 737, Advances in Experimental Medicine and Biology). Springer, New York, pp 175–179

  • Xu HN, Nioka S, Glickson J, Chance B, Li LZ (2010) Quantitative mitochondrial redox imaging of breast cancer metastatic potential. J Biomed Opt 15:036010

    Article  CAS  Google Scholar 

  • Xu HN, Tchou J, Chance B, Li LZ (2012) Imaging the redox states of human breast cancer core biopsies. Adv Exp Med Biol

  • Xu HN, Wu B, Nioka S, Chance B, Li LZ (2009a) Calibration of CCD-based redox imaging for biological tissues. Paper presented at the Proceedings of SPIE - Medical Imaging 2009: Biomedical Applications in Molecular, Structural, and Functional Imaging, Lake Buena Vista, FL, USA

  • Xu HN, Wu B, Nioka S, Chance B, Li LZ (2009b) Quantitative redox scanning of tissue samples using a calibration procedure. Journal of Innovative Optical Health Sciences 2:375–385

    Article  Google Scholar 

  • Xu HN, Zhou R, Nioka S, Chance B, Glickson JD, Li LZ (2009c) Histological basis of MR/optical imaging of human melanoma mouse xenografts spanning a range of metastatic potentials. Adv Exp Med Biol 645:247–253

    Article  Google Scholar 

  • Ying WH (2008) NAD(+)/ NADH and NADP(+)/NADPH in cellular functions and cell death: regulation and biological consequences. Antioxid Redox Signal 10(2):179–206

    Article  CAS  Google Scholar 

  • Zhang Q, Wang SY, Nottke AC, Rocheleau JV, Piston DW, Goodman RH (2006) Redox sensor CtBP mediates hypoxia-induced tumor cell migration. Proc Natl Acad Sci U S A 103(24):9029–9033

    Article  CAS  Google Scholar 

  • Zhang Z, Blessington D, Li H, Busch TM, Glickson J, Luo Q, Chance B, Zheng G (2004a) Redox ratio of mitochondria as an indicator for the response of photodynamic therapy. J Biomed Opt 9(4):772–778

    Article  CAS  Google Scholar 

  • Zhang ZH, Li H, Liu Q, Zhou LL, Zhang M, Luo QM, Glickson J, Chance B, Zheng G (2004b) Metabolic imaging of tumors using intrinsic and extrinsic fluorescent markers. Biosens Bioelectron 20(3):643–650

    Article  CAS  Google Scholar 

  • Zhu C, Burnside ES, Sisney GA, Salkowski LR, Harter JM, Yu B, Ramanujam N (2009) Fluorescence spectroscopy: an adjunct diagnostic tool to image-guided core needle biopsy of the breast. IEEE Trans Biomed Eng 56(10):2518–2528

    Article  Google Scholar 

  • Ziegler M (2005) A vital link between energy and signal transduction. Regulatory functions of NAD(P). FEBS J 272(18):4561–4564

    Article  CAS  Google Scholar 

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Correspondence to Lin Z. Li.

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Li, L.Z. Imaging mitochondrial redox potential and its possible link to tumor metastatic potential. J Bioenerg Biomembr 44, 645–653 (2012). https://doi.org/10.1007/s10863-012-9469-5

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