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

Dane M Wolf1,2, Mayuko Segawa1, Arun Kumar Kondadi3

  • 1Department of Medicine (Endocrinology), Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

The EMBO Journal
|October 15, 2019
PubMed

Insights

Mitochondrial inner membranes show distinct membrane potentials across cristae and boundary regions. This heterogeneity suggests cristae function as independent bioenergetic units, preventing widespread mitochondrial dysfunction.

Area of Science:

  • Cell Biology
  • Mitochondrial Biology
  • Bioenergetics

Background:

  • The mitochondrial membrane potential (ΔΨm) drives oxidative phosphorylation (OXPHOS).
  • The inner mitochondrial membrane (IMM) was traditionally viewed as having a uniform ΔΨm.
  • Cristae compartmentalize OXPHOS components, questioning the uniform ΔΨm model.

Purpose of the Study:

  • To investigate the spatial distribution of ΔΨm across the IMM at the cristae level.
  • To determine if individual cristae exhibit distinct membrane potentials.
  • To explore the functional implications of ΔΨm heterogeneity within mitochondria.

Main Methods:

  • Development of a novel approach to measure ΔΨm at the resolution of individual cristae.
  • Utilizing pharmacological agents (oligomycin, FCCP) to modulate ΔΨm.
  • Genetic manipulation affecting cristae structure (MICOS complex, Opa1 deletion).

Main Results:

  • The IMM exhibits segmented ΔΨm, with higher potentials in cristae compared to inner boundary membranes (IBM).
  • Oligomycin increased ΔΨm heterogeneity, while FCCP decreased it.
  • Disruption of cristae structure (MICOS, Opa1) reduced ΔΨm heterogeneity.
  • Individual cristae within a mitochondrion can display different membrane potentials.

Conclusions:

  • The IMM is not equipotential; distinct ΔΨm exist between cristae and IBM.
  • Cristae act as independent bioenergetic units within a mitochondrion.
  • This compartmentalization prevents the spread of dysfunction from individual cristae to the entire mitochondrion.
Keywords:
MICOS complexOpa1crista junctioncristaemembrane potential

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