Abstract
By manipulating the physical properties of oxygen, cells are able to harvest the large thermodynamic potential of oxidation to provide a substantial fraction of the energy necessary for cellular processes. The enzyme largely responsible for this oxygen manipulation is cytochrome c oxidase, which resides at the inner mitochondrial membrane. For unknown reasons, cancer cells do not maximally utilize this process, but instead rely more on an anaerobic-like metabolism demonstrating the so-called Warburg effect. As the enzyme at the crossroads of oxidative metabolism, cytochrome c oxidase might be expected to play a role in this so-called Warburg effect. Through protein assay methods and metabolic studies with radiolabeled glucose, alterations associated with cancer and cytochrome c oxidase subunit levels are explored. The implications of these findings for cancer research are discussed briefly.
Similar content being viewed by others
References
Bongaerts GP, van Halteren HK, Verhagen CA, Wagner DJ (2006) Med Hypotheses 67:1213–1222
Chesney J, Mitchell R, Benigni F, Bacher M, Spiegel L, Al-Abed Y, Han JH, Metz C, Bucala R (1999) Proc Natl Acad Sci USA 96:3047–3052
Collman JP, Herrmann PC, Boitrel B, Zhang X, Eberspacher TA, Fu L, Wang J, Rousseau DL, Williams ER (1994) J Am Chem Soc 116:9783–9784
Collman JP, Fu L, Herrmann PC, Zhang X (1997) Science 275:949–951
Collman JP, Fu L, Herrmann PC, Wang Z, Rapta M, Broring M, Schwenninger R, Boitrel B (1998) Angew Chem (Int Ed) 37:3397–3400
Collman JP, Boulatov R, Sunderland CJ, Fu L (2004) Chem Rev 104:561–588
Collman JP, Devaraj NK, Decreau RA, Yang Y, Yan YL, Ebina W, Eberspacher TA, Chidsey CED (2007) Science 315:1565–1568
Herrmann PC (1996) Synthetic models of cytochrome c oxidase and myoglobin. Dissertation, Stanford University Department of Chemistry, pp 1–28
Herrmann PC, Gillespie JW, Charboneau L, Bichsel VE, Paweletz CP, Calvert VS, Kohn EC, Emmert-Buck MR, Liotta LA, Petricoin EF III (2003) Proteomics 3:1801–1810
Hey Y, Hoggard N, Burt E, James LA, Varley JM (1997) Cytogenet Cell Genet 77:167–168
Hofmann S, Lichtner P, Schuffenhauser S, Gerbitz KD, Meitinger T (1998) Cytogenet Cell Genet 83:226–227
Holmes FL (1985) Lavoisier and the chemistry of life: an exploration of scientific creativity. University of Wisconsin Press, Madison
Kadenbach B, Huttemann M, Arnold S, Lee I, Bender E (2000) Free Radic Biol Med 29:211–221
Ko YH, Smith BL, Wang Y, Pomper MG, Rini DA, Torbenson MS, Hullihen J, Pedersen PL (2004) Biochem Biophys Res Commun 324:269–275
Krieg RC, Knuechel R, Schiffmann E, Liotta LA, Petricoin EF III, Herrmann PC (2004a) Proteomics 4:2789–2795
Krieg RC, Liotta LA, Petricoin EF III, Herrmann PC (2004b) J Biochem Biophys Methods 58:119–124
Lee N, Morin C, Mitchell G, Robinson BH (1998) Biochim Biophys Acta 1406:1–4
Mathupala SP, Rempel A, Pedersen PL (1997) J Bioenerg Biomembranes 29:339–343
Mathupala SP, Ko YH, Pedersen PL (2006) Oncogene 25:4777–4786
Nakashima RA, Paggi MG, Pedersen PL (1984) Cancer Res 44:5702–5706
Pedersen PL (1978) Prog Exp Tumor Res 22:190–274
Perrin A, Roudier E, Duborjal H, Bachelet C, Riva-Lavieille C, Leverve X, Massarelli R (2002) Biochimie 84:1003–1011
Tisdale MJ (1997) J Natl Cancer Inst 89:1763–1773
Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, ShinzawaItoh K, Nakashima R, Yaona R, Yoshikawa S (1996) Science 272:1136–1144
Vijayasarathy C, Biunno I, Lenka N, Yang M, Basu A, Hall IP, Avadhani NG (1998) Biochim Biophys Acta 1371:71–82
Warburg O (1925) Ber Dtsch Chem Ges 58:1001–1003
Warburg O (1929) Biochem Z 204:482–494
Warburg O (1930) Metabolism of tumors. Arnold Constable, London
Warburg O (1956) Science 123:309–314
Warburg O, Kubowitz F (1927) Biochem Z 189:242–249
Warburg O, Negelein E (1928) Biochem Z 193:334–339
Warburg O, Posenor K, Negelein E (1924) Biochem Z 152:309–345
Yanamara W, Zhang YZ, Takamiya S, Capaldi RA (1988) Biochemistry 27:4909–4914
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Herrmann, P.C., Herrmann, E.C. Oxygen metabolism and a potential role for cytochrome c oxidase in the Warburg effect. J Bioenerg Biomembr 39, 247–250 (2007). https://doi.org/10.1007/s10863-007-9084-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10863-007-9084-z