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Impaired Mitochondrial Metabolism and Mammary Carcinogenesis

  • Nagendra Yadava
  • Sallie S. Schneider
  • D. Joseph Jerry
  • Chul Kim
Article

Abstract

Mitochondrial oxidative metabolism plays a key role in meeting energetic demands of cells by oxidative phosphorylation (OxPhos). Here, we have briefly discussed (a) the dynamic relationship that exists among glycolysis, the tricarboxylic acid (TCA) cycle, and OxPhos; (b) the evidence of impaired OxPhos (i.e. mitochondrial dysfunction) in breast cancer; (c) the mechanisms by which mitochondrial dysfunction can predispose to cancer; and (d) the effects of host and environmental factors that can negatively affect mitochondrial function. We propose that impaired OxPhos could increase susceptibility to breast cancer via suppression of the p53 pathway, which plays a critical role in preventing tumorigenesis. OxPhos is sensitive to a large number of factors intrinsic to the host (e.g. inflammation) as well as environmental exposures (e.g. pesticides, herbicides and other compounds). Polymorphisms in over 143 genes can also influence the OxPhos system. Therefore, declining mitochondrial oxidative metabolism with age due to host and environmental exposures could be a common mechanism predisposing to cancer.

Keywords

Mitochondrial metabolism Oxidative phosphorylation OxPhos Inflammation Tumor suppressor p53 Breast cancer 

Abbreviations

NAD+ and NADH

Oxidized and reduced nicotinamide adenine dinucleotides, respectively

NADP+ and NADPH

Phosphorylated forms of NAD+ and NADH, respectively

ADP

Adenosine diphosphate

ATP

Adenosine triphosphate

Pi

Inorganic phosphate

FAD and FADH2

Oxidized and reduced flavin adenine dinucleotides, respectively

nDNA

Nuclear-DNA

mtDNA

Mitochondrial-DNA

OxPhos

Oxidative phosphorylation

TCA

Tricarboxylic acid

CoA

Coenzyme A

Notes

Acknowledgments

This work was supported by institutional start-up and translational funds from CEAR at the PVLSI supported by an award (A00000000004448) from Massachusetts Technology Collaborative as administrator of the John Adams Innovation Institute and an NIH grant (R21NS057224-01A2) to N. Y. We thank Maureen Lahti for critical reading of the manuscript.

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Nagendra Yadava
    • 1
    • 2
    • 3
  • Sallie S. Schneider
    • 1
    • 4
  • D. Joseph Jerry
    • 1
    • 4
  • Chul Kim
    • 1
  1. 1.Pioneer Valley Life Sciences InstituteSpringfieldUSA
  2. 2.Division of EndocrinologyDiabetes & Metabolism at Baystate Medical Center of Tufts University School of MedicineSpringfieldUSA
  3. 3.Department of BiologyUniversity of MassachusettsAmherstUSA
  4. 4.Department of Veterinary & Animal SciencesUniversity of MassachusettsAmherstUSA

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