Cytochrome c release from mitochondria proceeds by a two-step process

Cytochrome c is often released from mitochondria during the early stages of apoptosis, although the precise mechanisms regulating this event remain unclear. In this study, with isolated liver mitochondria, we demonstrate that cytochrome c release requires a two-step process. Because cytochrome c is present as loosely and tightly bound pools attached to the inner membrane by its association with cardiolipin, this interaction must first be disrupted to generate a soluble pool of this protein. Specifically, solubilization of cytochrome c involves a breaching of the electrostatic and/or hydrophobic affiliations that this protein usually maintains with cardiolipin. Once cytochrome c is solubilized, permeabilization…

• SF
  Swedish Foundation for International Cooperation in Research and Higher Education
• KI
  Karolinska Institutet
• UK
  Universität Konstanz
• NI
  National Institutes of Health
• MR
  Medical Research Council
• NC
  National Cancer Institute