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Cancer and Mitochondria

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Biochemistry of Oxidative Stress

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 16))

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Abstract

Cancer is a devastating pathology that involves symptoms, discomfort, family and social disintegration, and finally leads to a debilitating condition and death. It was Otto Warburg, the extraordinary German scientist, who opened our eyes towards the notion of the existence of a metabolic disruption in cancer cells. Since Warburg pioneering studies physicians and scientists had considered a role of mitochondria in the genesis of cancer. Mitochondria are ancient rickettsia incorporated as organelles into a primitive eukaryotic recipient cell. Mitochondria changed the primitive anaerobic metabolism to an oxygen dependent respiration that multiplied the energy production in cells from 2 to 36 moles of ATP by mol of utilized glucose. Therefore, this chapter is mainly directed to respond what happens to mitochondria in cancer. We will describe here the mitochondrial alterations reported in this pathology. The reader will realize that we favor the notion that mitochondrial dysfunction and the incorrect use of oxygen are factors associated to a particular cell development and function that at the same time is the mechanism of pathogenesis of a debilitating and mortal illness.

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References

  1. Klaunig JE, Kamendulis LM, Hocevar BA (2010) Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol 38:96–109

    Article  CAS  PubMed  Google Scholar 

  2. Koppenol WH, Bounds PL, Dang CV (2011) Otto Warburg’s contributions to current concepts of cancer metabolism. Nature Review Cancer 11:325–337

    Article  CAS  Google Scholar 

  3. Shen HM, Ong CN (1996) Mutation of the p53 tumor suppressor gene and ras oncogenes in aflatoxin hepatocarcinogenesis. Mutat Res 366:23–44

    Article  PubMed  Google Scholar 

  4. Fraga CG, Shigenaga MK, Park J-W et al (1990) Oxidative damage to DNA during aging: 8-hydroxy-deoxyguanosine in rat organ DNA and urine. Proc Natl Acad Sci U S A 87:4533–4537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lu J, Tan M, Cai Q (2015) The Warburg effect in tumor progression: mitochondrial oxidative metabolism as an anti-metastasis mechanism. Cancer Lett 356:156–164

    Article  CAS  PubMed  Google Scholar 

  6. Nunomura W, Takakuwa Y, Cherr GN et al (2007) Characterization of protein 4.1R in the erythrocytes of zebrafish (Danio rerio): unique binding properties with transmembrane proteins and calmodulin. Comp Biochem Physiol B Biochem Mol Biol 148:124–138

    Article  PubMed  Google Scholar 

  7. Uchida HK, Szweda I, Chae Z et al (1993) Immunochemical detection of 4-hydroxynonenal protein adducts in oxidized hepatocytes. Proc Natl Acad Sci U S A 90:8742–8746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nishigori C, Hattori Y, Toyokuni S (2004) Role of reactive oxygen species in skin carcinogenesis. Antioxid Redox Signal 6:561–570

    Article  CAS  PubMed  Google Scholar 

  9. Weiss KM (2005) The phenogenetic logic of life. Nat Rev Genet 6:36–45

    Article  CAS  PubMed  Google Scholar 

  10. Miyake T, Reese J, Loch CM et al (2004) Genome-wide analysis of ARS (autonomously replicating sequence) binding factor 1 (Abf1p)-mediated transcriptional regulation in Saccharomyces cerevisiae. J Biol Chem 279:34865–34872

    Article  CAS  PubMed  Google Scholar 

  11. Syslová K, Böhmová A, Mikoška M et al (2014) Multimarker screening of oxidative stress in aging. Oxid Med Cell Longev 2014:562860. doi:10.1155/2014/562860

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hwang ES, Bowen PE (2007) DNA damage, a biomarker of carcinogenesis: its measurement and modulation by diet and environment. Crit Rev Food Sci Nutr 47:27–50

    Article  CAS  PubMed  Google Scholar 

  13. Frenkel K (1992) Carcinogen-mediated oxidant formation and oxidative DNA damage. Pharmac Ther 53:127–166

    Article  CAS  Google Scholar 

  14. Demple B, Harrison L (1994) Repair of oxidative damage to DNA: enzymology and biology. Annu Rev Biochem 63:915–948

    Article  CAS  PubMed  Google Scholar 

  15. Shibutani S, Takeshita M, Grollman AP (1991) Insertion of specific bases during DNA synthesis past the oxidation damaged base 8-oxodG. Nature 349:431–444

    Article  CAS  PubMed  Google Scholar 

  16. Gredilla R, Bohr VA, Stevnsner T (2010) Mitochondrial DNA repair and association with aging: an update. Exp Gerontol 45:478–488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Gao Y, Dickerson JB, Guo F et al (2004) Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci U S A 101:7618–7623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kawanishi S, Hiraku Y (2006) Oxidative and nitrative DNA damage as biomarker for carcinogenesis with special reference to inflammation. Antioxid Redox Signal 8:1047–1058

    Article  CAS  PubMed  Google Scholar 

  19. Evans MD, Dizdaroglu M, Cooke M (2004) Oxidative DNA damage and disease: induction, repair and significance. Mutat Res 567:1–61

    Article  CAS  PubMed  Google Scholar 

  20. Liu RH (2004) Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr 134:3479S–3485S

    CAS  PubMed  Google Scholar 

  21. Ishikawa K, Takenaga K, Akimoto M et al (2008) ROS generating mitochondrial DNA mutations regulate tumor cell metastasis. Science 320:661–664

    Article  CAS  PubMed  Google Scholar 

  22. Frank GD, Mifune M, Inagami T et al (2003) Distinct mechanisms of receptor and nonreceptor tyrosine kinase activation by reactive oxygen species in vascular smooth muscle cells: role of metalloprotease and protein kinase C-delta. Mol Cell Biol 235:1581–1589

    Article  Google Scholar 

  23. Lin D, Takemoto DJ (2005) Oxidative activation of protein kinase C gamma through the C1 domain. Effects on gap junctions. J Biol Chem 280:13682–13693

    Article  CAS  PubMed  Google Scholar 

  24. Gopalakrishna R, Anderson WB (1989) Ca2+ and phospholipid independent activation of protein kinase C by selective oxidative modification of the regulatory domain. Proc Natl Acad Sci 86:6758–6762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kensler TW, Wakabayashi N, Biswal S (2007) Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol 47:89–116

    Article  CAS  PubMed  Google Scholar 

  26. Benhar M, Engelberg D, Levitzki A (2002) ROS, stress-activated kinases and stress signaling in cancer. EMBO Rep 3:420–425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rankin EB, Giaccia AJ (2008) The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ 15:678–685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Warburg O (1956) On the origin of cancer cells. Science 123:309–314

    Article  CAS  PubMed  Google Scholar 

  29. Arner ES, Holmgren A (2000) Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem 267:6102–6109

    Article  CAS  PubMed  Google Scholar 

  30. Dunbar DR, Moonie PA, Jacobs HT et al (1995) Different cellular back-grounds confer a marked advantage to either mutant or wild-type mitochondrial genomes. Proc Natl Acad Sci U S A 92:6562–6566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nishikawa M, Nishiguchi S, Shiomi S et al (2001) Somatic mutation of mitochondrial DNA in cancerous and noncancerous liver tissue in individuals with hepatocellular carcinoma. Cancer Res 61:1843–1845

    CAS  PubMed  Google Scholar 

  32. Lievre A, Blons H, Houllier AM et al (2006) Clinicopathological significance of mitochondrial D-Loop mutations in head and neck carcinoma. Br J Cancer 94:692–697

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Prior SL, Griffiths AP, Baxter JM et al (2006) Mitochondrial DNA mutations in oral squamous cell carcinoma. Carcinogenesis 27:945–950

    Article  CAS  PubMed  Google Scholar 

  34. He Y, Wu J, Dressman DC et al (2010) Heteroplasmic mitochondrial DNA mutations in normal and tumour cells. Nature 464:610–614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Coller HA, Khrapko K, Bodyak ND et al (2001) High frequency of homoplasmic mitochondrial DNA mutations in human tumors can be explained without selection. Nat Genet 28:147–150

    Article  CAS  PubMed  Google Scholar 

  36. Chatterjee A, Dasgupta S, Sidransky D (2011) Mitochondrial subversion in cancer. Cancer Prev Res (Phila) 4:638–654

    Article  CAS  Google Scholar 

  37. Wheelhouse NM, Lai PB, Wigmore SJ et al (2005) Mitochondrial D-loop mutations and deletion profiles of cancerous and noncancerous liver tissue in hepatitis B virus-infected liver. Br J Cancer 92:1268–1272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gochhait S, Bhatt A, Sharma S et al (2008) Concomitant presence of mutations in mitochondrial genome and p53 in cancer development: a study in north India sporadic breast and esophageal cancer patients. Int J Cancer 123:2580–2586

    Article  CAS  PubMed  Google Scholar 

  39. Carew JS, Zhou Y, Albitar M et al (2003) Mitochondrial DNA mutations in primary leukemia cells after chemotherapy: clinical significance and therapeutic implications. Leukemia 17:1437–1447

    Article  CAS  PubMed  Google Scholar 

  40. Maitra A, Cohen Y, Gillespie SE et al (2004) The Human MitoChip: a high-throughput sequencing nicroarray for mitochondrial mutation detection. Genome Res 14:812–819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hung WY, Lin JC, Lee LM et al (2008) Tandem duplication- triplication correlated with poly-cytosine stretch variation in human mitochondrial DNA D-loop region. Mutagenesis 23:137–142

    Article  CAS  PubMed  Google Scholar 

  42. Sanchez-Pino MJ, Moreno P, Navarro A (2007) Mitochondrial dysfunction in human colorectal cancer progression. Front Biosci 12:1190–1199

    Article  CAS  PubMed  Google Scholar 

  43. Sanchez-Cespedes M, Parrella P, Nomoto S et al (2001) Identification of a nucleotide repeat as a major target for mitochondrial DNA alterations in human tumors. Cancer Res 61:7015–7019

    CAS  PubMed  Google Scholar 

  44. Galli S, Labato MI, Bal de Kier JE et al (2003) Decreased mitochondrial nitric oxide activity and hydrogen peroxide relate persistent tumoral proliferation to embryonic behavior. Cancer Res 63:6370–6377

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Instituto de Inmunología, Genética y Metabolismo (INIGEM, UBA–CONICET), Laboratorio de Metabolismo del Oxígeno, Hospital Universitario, Universidad de Buenos Aires, Buenos Aires, Argentina

    Juan José Poderoso

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  1. Juan José Poderoso
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Correspondence to Juan José Poderoso .

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Editors and Affiliations

  1. School of Medicine, University of Buenos Aires, Buenos Aires, Argentina

    Ricardo Jorge Gelpi

  2. School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina

    Alberto Boveris

  3. Instituto de Inmunología, Genética y Metabolismo (INIGEM, UBA–CONICET), Laboratorio de Metabolismo del Oxígeno, Hospital Universitario, Universidad de Buenos Aires, Buenos Aires, Argentina

    Juan José Poderoso

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Poderoso, J.J. (2016). Cancer and Mitochondria. In: Gelpi, R., Boveris, A., Poderoso, J. (eds) Biochemistry of Oxidative Stress. Advances in Biochemistry in Health and Disease, vol 16. Springer, Cham. https://doi.org/10.1007/978-3-319-45865-6_26

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