Complex III Releases Superoxide to Both Sides of the Inner Mitochondrial Membrane

In the present report ), we address previous experimental shortcomings and we challenge the newly popular opinion that Complex III only releases superoxide to the cytoplasmic side of the inner membrane

Florian L. Muller

2004

Scholarcy highlights

  • The mitochondrial electron transport chain is the main source of ATP in the mammalian cell and is essential for life
  • During energy transduction, a small number of electrons “leak” to oxygen prematurely, forming the oxygen free radical superoxide, which has been implicated in the pathophysiology of a variety of diseases including Parkinson’s, Hun
  • While an increasing number of investigators have focused their attention on the potential pathological effects of mitochondrial superoxide, there is a dearth of information on the mechanisms of deleterious superoxide formation by the electron transport chain
  • The first studies on electron transport chain-derived superoxide production concluded that most superoxide must be extruded to the matrix side since superoxide was readily released from antimycin A- or rotenone-treated submitochondrial particles but not from intact mitochondria
  • In the present report, we address previous experimental shortcomings and we challenge the newly popular opinion that Complex III only releases superoxide to the cytoplasmic side of the inner membrane
  • Using direct methods of superoxide detection, we failed to observe a significant increase in superoxide release from intact skeletal muscle mitochondria in response to the addition of rotenone with glutamate/malate
  • Given the fact that superoxide is very selective in its targets and that once released into a membrane-bound compartment it cannot escape, understanding the sidedness of superoxide release by its sites of generation is essential to clarify the role of mitochondrial superoxide production in pathophysiology
  • Having demonstrated that the Qo site of Complex III releases superoxide toward both the mitochondrial matrix and the IMS, we argue that at present the two hypotheses we put forward best explain this observation

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