Loss of mitochondrial membrane potential is associated with increase in mitochondrial volume: physiological role in neurones

J Cell Physiol. 2006 Feb;206(2):347-53. doi: 10.1002/jcp.20476.


Mitochondrial volume homeostasis is a housekeeping cellular function, thought to help regulate oxidative capacity, apoptosis, and mechanical signaling. The volume is mainly regulated by potassium flux into and out of the matrix and controlled by the electrochemical potential. Mitochondrial depolarization will therefore affect this flux but studies showing how have not been consistent, and it is unclear what mitochondrial volume changes also occur. The aim of the present study was to investigate mitochondrial volume changes in permeabilized neurons under various bioenergetic conditions using deconvolution confocal microscopy. Under control conditions, mitochondria in situ appeared rod-shaped with mean length, surface area, and volume values of 2.29+/-0.10 microm, 1.41+/-0.10 microm2, and 0.062+/-0.006 microm3, respectively (n=42). Valinomycin, a K+-selective ionophore, increased mitochondrial volume by 63+/-22%, although surface area was almost unchanged because mitochondrial shape became more spherical. Pinacidil, an opener of mitochondrial ATP-dependent channels, produced similar effects, although some mitochondria were insensitive to its action. Mitochondrial depolarization with the protonophore FCCP, or with respiratory chain inhibitors antimycin and sodium azide was associated with a considerable increase in mitochondrial volume (by 75%-140%). Effects of mitochondrial modulators were also studied in intact neurones. Tracking of single mitochondria showed that during 65+/-2% of their time, mitochondria were motile with an average velocity of 0.19+/-0.01 microm/s. Antimycin, azide, and FCCP induced mitochondrial swelling and significantly decreased mitochondrial motility. In the presence of pinacidil, swollen mitochondria had reduced their motility, although mitochondria with normal volume stayed motile. These data show that mitochondrial depolarization was followed by significant swelling, which, in turn, impaired mitochondrial trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azides / pharmacology
  • Brain / cytology
  • Cell Movement / drug effects
  • Cells, Cultured
  • Macrolides / pharmacology
  • Membrane Potentials*
  • Microscopy, Confocal / methods
  • Mitochondria / ultrastructure
  • Mitochondrial Membranes / drug effects*
  • Mitochondrial Swelling*
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Pinacidil / pharmacology
  • Rats
  • Rats, Wistar
  • Valinomycin / pharmacology*


  • Azides
  • Macrolides
  • Valinomycin
  • Pinacidil