On the Mechanism of Sustained Mitochondrial Membrane Potential Without Functioning Complex IV

Adv Exp Med Biol. 2022:1395:367-372. doi: 10.1007/978-3-031-14190-4_60.

Abstract

In intact mitochondria, the transport of electrons, respiration and generation of proton gradients across the inner membrane (proton motive force) are mutually coupled, according to Peter Mitchell's hypothesis on oxidative phosphorylation. Thus, the inhibition of electron transport at either respiratory complex III or IV in the electron transport chain leads to failure in producing proton motive force along with the abolition of respiration. Here, we determined the mitochondrial membrane potential (MMP), as a measure of proton motive force, and cellular respiration in various cultured cells and demonstrated that inhibition of complex IV by KCN abolished mitochondrial respiration while MMP was sustained. These results are unexpected and appear incompatible with Mitchell's chemiosmotic hypothesis.

Keywords: Electron transport; Mitchell’s chemiosmotic hypothesis; Mitochondria; Proton motive force.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Electron Transport Complex IV* / metabolism
  • Membrane Potential, Mitochondrial
  • Mitochondrial Membranes / metabolism
  • Oxidative Phosphorylation
  • Proton-Motive Force*

Substances

  • Electron Transport Complex IV
  • Adenosine Triphosphate