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

Dane M. Wolf, Mayuko Segawa, Arun Kumar Kondadi, Ruchika Anand, Sean T. Bailey, Andreas S. Reichert, Alexander M. van der Bliek, David B. Shackelford, Marc Liesa, Orian S. Shirihai

Research output: Contribution to journalArticlepeer-review

190 Scopus citations


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.

Original languageEnglish
Article numbere101056
JournalEMBO Journal
Issue number22
StatePublished - 15 Nov 2019
Externally publishedYes


  • MICOS complex
  • Opa1
  • crista junction
  • cristae
  • membrane potential

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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