Calcium-induced Cytochrome c release from rat brain mitochondria is altered by digitonin

Neurosci Lett. 2002 Oct 31;332(2):91-4. doi: 10.1016/s0304-3940(02)00948-5.


To determine if calcium could release Cytochrome c (Cyt c) from brain mitochondria without activating the permeability transition (mPT), brain mitochondria were prepared in two different ways. Digitonin was used to lyse synaptosomes and release synaptosomal mitochondria or a Percoll gradient was used to separate non-synaptosomal mitochondria from the synaptosomes. In gradient-purified mitochondria, low levels of added digitonin produced swelling and Cyt c release. Digitonin augmented Ca(2+)-induced Cyt c release that was insensitive to the mPT inhibitors, cyclosporin A CsA and ADP. Similarly, in mitochondria prepared with digitonin, these inhibitors also failed to prevent Ca(2+)-induced Cyt c release. Thus the mPT-independent, Ca(2+)-induced Cyt c release pathway was attributable to alteration of the permeability properties of the outer mitochondrial membrane by digitonin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Chemistry / drug effects*
  • Calcium / pharmacology*
  • Culture Media
  • Cytochrome c Group / metabolism*
  • Digitonin / pharmacology*
  • In Vitro Techniques
  • Mannitol / pharmacology
  • Membrane Potentials / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondrial Swelling / drug effects
  • Rats
  • Sucrose / pharmacology


  • Culture Media
  • Cytochrome c Group
  • Mannitol
  • Sucrose
  • Digitonin
  • Calcium