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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
The EMBO journal | 2019

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.

Pubmed ID: 31609012

Associated grants

  • Agency: Medical Faculty, Heinrich Heine University Dusseldorf, International
    Id: FoKo-37/2015 and Foko-02/2015
  • Agency: Deutsche Forschungsgemeinschaft (DFG), International
    Id: SFB 974 Project B09
  • Agency: HHS | National Institutes of Health (NIH), International
    Id: R01 CA208642-01
  • Agency: HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), International
    Id: RO1DK099618-02
  • Agency: Deutsche Forschungsgemeinschaft (DFG), International
    Id: RE 1575/2-1
  • Agency: NHLBI NIH HHS, United States
    Id: T32 HL072752
  • Agency: NCI NIH HHS, United States
    Id: R01 CA208642
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK063491
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK099618

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