Disruption of the M80-Fe ligation stimulates the translocation of cytochrome c to the cytoplasm and nucleus in nonapoptotic cells

Native cytochrome c (cyt c) has a compact tertiary structure with a hexacoordinated heme iron and functions in electron transport in mitochondria and apoptosis in the cytoplasm. However, the possibility that protein modifications confer additional functions to cyt c has not been explored. Disruption...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-02, Vol.106 (8), p.2653-2658
Main Authors: Godoy, Luiz C, Muñoz-Pinedo, Cristina, Castro, Laura, Cardaci, Simone, Schonhoff, Christopher M, King, Michael, Tórtora, Verónica, Marín, Mónica, Miao, Qian, Jiang, Jian Fei, Kapralov, Alexandr, Jemmerson, Ronald, Silkstone, Gary G, Patel, Jinal N, Evans, James E, Wilson, Michael T, Green, Douglas R, Kagan, Valerian E, Radi, Rafael, Mannick, Joan B
Format: Article
Language:English
Subjects:
Antibodies
Apoptosis
Biochemistry
Biological Sciences
Cardiolipins
Cell Nucleus - enzymology
Cells
Cells, Cultured
Cytochromes
Cytochromes c - genetics
Cytochromes c - metabolism
Cytoplasm
Cytoplasm - enzymology
Enzyme kinetics
Fluorescent Antibody Technique
Green Fluorescent Proteins - genetics
HeLa Cells
Humans
Iron - metabolism
Ligation
Mitochondria
Nitration
Oxidative stress
Proteins
RNA, Small Interfering
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Native cytochrome c (cyt c) has a compact tertiary structure with a hexacoordinated heme iron and functions in electron transport in mitochondria and apoptosis in the cytoplasm. However, the possibility that protein modifications confer additional functions to cyt c has not been explored. Disruption of methionine 80 (M80)-Fe ligation of cyt c under nitrative stress has been reported. To model this alteration and determine if it confers new properties to cyt c, a cyt c mutant (M80A) was constitutively expressed in cells. M80A-cyt c has increased peroxidase activity and is spontaneously released from mitochondria, translocating to the cytoplasm and nucleus in the absence of apoptosis. Moreover, M80A models endogenously nitrated cyt c because nitration of WT-cyt c is associated with its translocation to the cytoplasm and nucleus. Further, M80A cyt c may up-regulate protective responses to nitrative stress. Our findings raise the possibility that endogenous protein modifications that disrupt the M80-Fe ligation (such as tyrosine nitration) stimulate nuclear translocation and confer new functions to cyt c in nonapoptotic cells.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0809279106