Individual cristae within the same mitochondrion display different membrane potentials and are functionally independent

EMBO J. 2019 Nov 15;38(22):e101056. doi: 10.15252/embj.2018101056. Epub 2019 Oct 14.


The mitochondrial membrane potential (ΔΨm ) is the main driver of oxidative phosphorylation (OXPHOS). The inner mitochondrial membrane (IMM), consisting of cristae and inner boundary membranes (IBM), is considered to carry a uniform ΔΨm . However, sequestration of OXPHOS components in cristae membranes necessitates a re-examination of the equipotential representation of the IMM. We developed an approach to monitor ΔΨm at the resolution of individual cristae. We found that the IMM was divided into segments with distinct ΔΨm , corresponding to cristae and IBM. ΔΨm was higher at cristae compared to IBM. Treatment with oligomycin increased, whereas FCCP decreased, ΔΨm heterogeneity along the IMM. Impairment of cristae structure through deletion of MICOS-complex components or Opa1 diminished this intramitochondrial heterogeneity of ΔΨm . Lastly, we determined that different cristae within the individual mitochondrion can have disparate membrane potentials and that interventions causing acute depolarization may affect some cristae while sparing others. Altogether, our data support a new model in which cristae within the same mitochondrion behave as independent bioenergetic units, preventing the failure of specific cristae from spreading dysfunction to the rest.

Keywords: MICOS complex; Opa1; crista junction; cristae; membrane potential.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cells, Cultured
  • Female
  • HeLa Cells
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Membrane Potential, Mitochondrial*
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / physiology*
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Proteins / metabolism
  • Myoblasts / cytology
  • Myoblasts / metabolism*
  • Oxidative Phosphorylation


  • Mitochondrial Proteins
  • Adenosine Triphosphate