Nuclear translocation of cytochrome c during apoptosis.
Release of cytochrome c from mitochondria is a major event during apoptosis. Released cytochrome c has been shown to activate caspase-dependent apoptotic signals. In this report, we provide evidence for a novel role of cytochrome c in caspase-independent nuclear apoptosis. We showed that cytochrome c, released from mitochondria upon apoptosis induction, gradually accumulates in the nucleus as evidenced by both immunofluorescence and subcellular fractionation. Parallel to nuclear accumulation of cytochrome c, acetylated histone H2A, but not unmodified H2A, was released from the nucleus to the cytoplasm. Addition of purified cytochrome c to isolated nuclei recapitulated the preferential release of acetylated, but not deacetylated, histone H2A. Cytochrome c was also found to induce chromatin condensation. These results suggest that the nuclear accumulation of cytochrome c may be directly involved in the remodeling of chromatin. Our results provide evidence of a novel role for cytochrome c in inducing nuclear apoptosis.
Nur-E-Kamal
Alam
A
Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. nurekasa@umdnj.edu
Gross
Stephane R
SR
Pan
Zui
Z
Balklava
Zita
Z
Ma
Jianjie
J
Liu
Leroy F
LF
D021581:Active Transport, Cell Nucleus; D017209:Apoptosis; D020169:Caspases / Q000502:physiology; D002467:Cell Nucleus / Q000473:pathology*; D045304:Cytochromes c / Q000502:physiology*; D004789:Enzyme Activation; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D021381:Protein Transport
D006657:Histones; D045304:Cytochromes c; D020169:Caspases