Regulation of oxidative phosphorylation, the mitochondrial membrane potential, and their role in human disease

  • Maik Hüttemann
  • Icksoo Lee
  • Alena Pecinova
  • Petr Pecina
  • Karin Przyklenk
  • Jeffrey W. Doan


Thirty years after Peter Mitchell was awarded the Nobel Prize for the chemiosmotic hypothesis, which links the mitochondrial membrane potential generated by the proton pumps of the electron transport chain to ATP production by ATP synthase, the molecular players involved once again attract attention. This is so because medical research increasingly recognizes mitochondrial dysfunction as a major factor in the pathology of numerous human diseases, including diabetes, cancer, neurodegenerative diseases, and ischemia reperfusion injury. We propose a model linking mitochondrial oxidative phosphorylation (OxPhos) to human disease, through a lack of energy, excessive free radical production, or a combination of both. We discuss the regulation of OxPhos by cell signaling pathways as a main regulatory mechanism in higher organisms, which in turn determines the magnitude of the mitochondrial membrane potential: if too low, ATP production cannot meet demand, and if too high, free radicals are produced. This model is presented in light of the recently emerging understanding of mechanisms that regulate mammalian cytochrome c oxidase and its substrate cytochrome c as representative enzymes for the entire OxPhos system.


Apoptosis Cell signaling Cytochrome c Cytochrome c oxidase Ischemia reperfusion injury Mitochondria Membrane potential Neurodegenerative diseases Oxidative phosphorylation Reactive oxygen species 


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Maik Hüttemann
    • 1
  • Icksoo Lee
    • 1
  • Alena Pecinova
    • 1
  • Petr Pecina
    • 1
  • Karin Przyklenk
    • 2
  • Jeffrey W. Doan
    • 1
  1. 1.Center for Molecular Medicine and GeneticsWayne State University School of MedicineDetroitUSA
  2. 2.Cardiovascular Research InstituteWayne State University School of MedicineDetroitUSA

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