Disruption of the M80-Fe ligation stimulates the translocation of cytochrome c to the cytoplasm and nucleus in nonapoptotic cells
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.
UMass Chan Affiliations
Department of Cell BiologyDepartment of Biochemistry and Molecular Pharmacology
Department of Medicine, Division of Infectious Diseases and Immunology
Document Type
Journal ArticlePublication Date
2009-02-07Keywords
ApoptosisCell Nucleus
Cells, Cultured
Cytochromes c
Cytoplasm
Fluorescent Antibody Technique
Green Fluorescent Proteins
Hela Cells
Humans
Iron
RNA, Small Interfering
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2653-8. Epub 2009 Feb 5. Link to article on publisher's site
DOI
10.1073/pnas.0809279106Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39411PubMed ID
19196960Related Resources
ae974a485f413a2113503eed53cd6c53
10.1073/pnas.0809279106