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

Abstract

The mitochondrial membrane potential (ΔΨ m ) 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 ΔΨ m . 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 ΔΨ m at the resolution of individual cristae. We found that the IMM was divided into segments with distinct ΔΨ m , corresponding to cristae and IBM. ΔΨ m was higher at cristae compared to IBM. Treatment with oligomycin increased, whereas FCCP decreased, ΔΨ m heterogeneity along the IMM. Impairment of cristae structure through deletion of MICOS‐complex components or Opa1 diminished this intramitochondrial heterogeneity of ΔΨ m . 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.