title: The role of mitochondrial electron transport in tumorigenesis and metastasis.
abstract: BACKGROUND
  Tumor formation and spread via the circulatory and lymphatic drainage systems is associated with metabolic reprogramming that often includes increased glycolytic metabolism relative to mitochondrial energy production. However, cells within a tumor are not identical due to genetic change, clonal evolution and layers of epigenetic reprogramming. In addition, cell hierarchy impinges on metabolic status while tumor cell phenotype and metabolic status will be influenced by the local microenvironment including stromal cells, developing blood and lymphatic vessels and innate and adaptive immune cells. Mitochondrial mutations and changes in mitochondrial electron transport contribute to metabolic remodeling in cancer in ways that are poorly understood.
  
  
  METHODS
  This review concerns the role of mitochondria, mitochondrial mutations and mitochondrial electron transport function in tumorigenesis and metastasis.
  
  
  CONCLUSIONS
  It is concluded that mitochondrial electron transport is required for tumor initiation, growth and metastasis. Nevertheless, defects in mitochondrial electron transport that compromise mitochondrial energy metabolism can contribute to tumor formation and spread. These apparently contradictory phenomena can be reconciled by cells in individual tumors in a particular environment adapting dynamically to optimally balance mitochondrial genome changes and bioenergetic status.
  
  
  CONCLUSIONS
  Tumors are complex evolving biological systems characterized by genetic and adaptive epigenetic changes. Understanding the complexity of these changes in terms of bioenergetics and metabolic changes will permit the development of better combination anticancer therapies. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.
authors.affiliation: Malaghan Institute of Medical Research, PO Box 7060, Wellington 6242, New Zealand.
authors.forename: An S
authors.initials: AS
authors.lastname: Tan
authors.affiliation: Malaghan Institute of Medical Research, PO Box 7060, Wellington 6242, New Zealand.
authors.forename: James W
authors.initials: JW
authors.lastname: Baty
authors.affiliation: Malaghan Institute of Medical Research, PO Box 7060, Wellington 6242, New Zealand. Electronic address: mberridge@malaghan.org.nz.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Berridge
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D004579:Electron Transport / Q000235:genetics*; D006801:Humans; D008928:Mitochondria / Q000235:genetics*; D009154:Mutation; D009362:Neoplasm Metastasis / Q000235:genetics*; D059016:Tumor Microenvironment
keywords: Metabolic flexibility; Metastasis; Mitochondrial electron transport; Mitochondrial mutation; Mitochondrial respiration; Tumorigenesis