Journal of Bioenergetics and Biomembranes

, Volume 39, Issue 3, pp 243–246 | Cite as

A pivotal role for p53: balancing aerobic respiration and glycolysis

  • Wenzhe Ma
  • Ho Joong Sung
  • Joon Y. Park
  • Satoaki Matoba
  • Paul M. Hwang
Mini Review

Abstract

The genetic basis of increased glycolytic activity observed in cancer cells is likely to be the result of complex interactions of multiple regulatory pathways. Here we review the recent evidence of a simple genetic mechanism by which tumor suppressor p53 regulates mitochondrial respiration with secondary changes in glycolysis that are reminiscent of the Warburg effect. The biological significance of this regulation of the two major pathways of energy generation by p53 remains to be seen.

Keywords

Synthesis of cytochrome c oxidase 2 Cytochrome c oxidase Tumor protein p53 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, Gottlieb E, Vousden KH (2006) TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 126:107–120CrossRefGoogle Scholar
  2. Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, Sedivy JM, Kinzler KW, Vogelstein B (1998) Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 282:1497–1501CrossRefGoogle Scholar
  3. Bustamante E, Pedersen PL (1977) High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase. Proc Natl Acad Sci USA 74:3735–3739CrossRefGoogle Scholar
  4. Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR, Zhuang H, Cinalli RM, Alavi A, Rudin CM, Thompson CB (2004) Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 64:3892–3899CrossRefGoogle Scholar
  5. Feng Z, Zhang H, Levine AJ, Jin S (2005) The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci USA 102:8204–8209CrossRefGoogle Scholar
  6. Heerdt BG, Halsey HK, Lipkin M, Augenlicht LH (1990) Expression of mitochondrial cytochrome c oxidase in human colonic cell differentiation, transformation, and risk for colonic cancer. Cancer Res 50:1596–1600Google Scholar
  7. Herrmann PC, Gillespie JW, Charboneau L, Bichsel VE, Paweletz CP, Calvert VS, Kohn EC, Emmert-Buck MR, Liotta LA, Petricoin EF III (2003) Mitochondrial proteome: altered cytochrome c oxidase subunit levels in prostate cancer. Proteomics 3:1801–1810CrossRefGoogle Scholar
  8. Hofseth LJ, Hussain SP, Harris CC (2004) p53: 25 years after its discovery. Trends Pharmacol Sci 25:177–181CrossRefGoogle Scholar
  9. Ibrahim MM, Razmara M, Nguyen D, Donahue RJ, Wubah JA, Knudsen TB (1998) Biochimica et Biophysica Acta (BBA). Mol Cell Res 1403:254–264Google Scholar
  10. Jones RG, Plas DR, Kubek S, Buzzai M, Mu J, Xu Y, Birnbaum MJ, Thompson CB (2005) AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 18:283–293CrossRefGoogle Scholar
  11. Kondoh H, Lleonart ME, Gil J, Wang J, Degan P, Peters G, Martinez D, Carnero A, Beach D (2005) Glycolytic enzymes can modulate cellular life span. Cancer Res 65:177–185Google Scholar
  12. Li F, Wang Y, Zeller KI, Potter JJ, Wonsey DR, O’Donnell KA, Kim JW, Yustein JT, Lee LA, Dang CV (2005) Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis. Mol Cell Biol 25:6225–6234CrossRefGoogle Scholar
  13. Luciakova K, Kuzela S (1992) Increased steady-state levels of several mitochondrial and nuclear gene transcripts in rat hepatoma with a low content of mitochondria. Eur J Biochem 205:1187–1193CrossRefGoogle Scholar
  14. Mathupala SP, Heese C, Pedersen PL (1997) Glucose catabolism in cancer cells. The type II hexokinase promoter contains functionally active response elements for the tumor suppressor p53. J Biol Chem 272:22776–22780CrossRefGoogle Scholar
  15. Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F, Hwang PM (2006) p53 regulates mitochondrial respiration. Science 312:1650–1653CrossRefGoogle Scholar
  16. Modica-Napolitano JS, Singh KK (2004) Mitochondrial dysfunction in cancer. Mitochondrion 4:755–762CrossRefGoogle Scholar
  17. Okamura S, Ng CC, Koyama K, Takei Y, Arakawa H, Monden M, Nakamura Y (1999) Identification of seven genes regulated by wild-type p53 in a colon cancer cell line carrying a well-controlled wild-type p53 expression system. Oncol Res 11:281–285Google Scholar
  18. Olivier M, Eeles R, Hollstein M, Khan MA, Harris CC, Hainaut P (2002) The IARC TP53 database: new online mutation analysis and recommendations to users. Hum Mutat 19:607–614CrossRefGoogle Scholar
  19. Polyak K, Li Y, Zhu H, Lengauer C, Willson JK, Markowitz SD, Trush MA, Kinzler KW, Vogelstein B (1998) Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat Genet 20:291–293CrossRefGoogle Scholar
  20. Ruiz-Lozano P, Hixon ML, Wagner MW, Flores AI, Ikawa S, Baldwin AS Jr, Chien KR, Gualberto A (1999) p53 is a transcriptional activator of the muscle-specific phosphoglycerate mutase gene and contributes in vivo to the control of its cardiac expression. Cell Growth Differ 10:295–306Google Scholar
  21. Sariban-Sohraby S, Magrath IT, Balaban RS (1983) Comparison of energy metabolism in human normal and neoplastic (Burkitt’s lymphoma) lymphoid cells. Cancer Res 43:4662–4664Google Scholar
  22. Schuhmacher M, Staege MS, Pajic A, Polack A, Weidle UH, Bornkamm GW, Eick D, Kohlhuber F (1999) Control of cell growth by c-Myc in the absence of cell division. Curr Biol 9:1255–1258CrossRefGoogle Scholar
  23. Schulz TJ, Thierbach R, Voigt A, Drewes G, Mietzner B, Steinberg P, Pfeiffer AF, Ristow M (2006) Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth: Otto Warburg revisited. J Biol Chem 281:977–981CrossRefGoogle Scholar
  24. Schwartzenberg-Bar-Yoseph F, Armoni M, Karnieli E (2004) The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res 64:2627–2633CrossRefGoogle Scholar
  25. Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10:789–799CrossRefGoogle Scholar
  26. Warburg O (1956) Science 123:309–314CrossRefGoogle Scholar
  27. Zhou S, Kachhap S, Singh KK (2003) Mitochondrial impairment in p53-deficient human cancer cells. Mutagenesis 18:287–292CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Wenzhe Ma
    • 1
  • Ho Joong Sung
    • 1
  • Joon Y. Park
    • 1
  • Satoaki Matoba
    • 2
  • Paul M. Hwang
    • 1
  1. 1.Cardiology Branch, National Heart, Lung, and Blood InstituteNational Institutes of HealthBethesdaUSA
  2. 2.Department of Cardiovascular MedicineKyoto Prefectural University of MedicineKyotoJapan

Personalised recommendations