Activation of NO donors in mitochondria:: Peroxidase metabolism of (2-hydroxyamino-vinyl)-triphenyl-phosphonium by cytochrome c releases NO and protects cells against apoptosis

In mitochondrial apoptosis, the formation of cytochrome c-cardiolipin complex ([CL-cyt c]) with peroxidase properties is an early event in the cascade of reactions that leads to cell death. Herein, we report the synthesis of a new prodrug, (2-hydroxyamino-vinyl)-triphenyl-phosphonium (HVTP), which compartmentalizes exclusively into mitochondria, undergoes a [CL-cyt c]-catalyzed bioactivation to nitric oxide (NO), inhibits peroxidase activity, and protects cells from apoptosis. (c) 2008 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.