title: Impaired mitochondrial metabolism and mammary carcinogenesis.
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.
authors.affiliation: Pioneer Valley Life Sciences Institute, Springfield, MA 01107, USA. Nagendra.Yadava@baystatehealth.org
authors.forename: Nagendra
authors.initials: N
authors.lastname: Yadava
authors.forename: Sallie S
authors.initials: SS
authors.lastname: Schneider
authors.forename: D Joseph
authors.initials: DJ
authors.lastname: Jerry
authors.forename: Chul
authors.initials: C
authors.lastname: Kim
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D002274:Carcinogens, Environmental / Q000633:toxicity; D004198:Disease Susceptibility / Q000139:chemically induced / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism; D042361:Mammary Glands, Human / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects
chemical_list: D002274:Carcinogens, Environmental