Disruption of the M80-Fe ligation stimulates the translocation of cytochrome c to the cytoplasm and nucleus in nonapoptotic cells
Department of Medicine, Division of Infectious Diseases and Immunology; Department of Biochemistry and Molecular Pharmacology; Department of Cell Biology
Apoptosis; Cell 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
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.
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Citation: 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
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; and Mannick, Joan B., "Disruption of the M80-Fe ligation stimulates the translocation of cytochrome c to the cytoplasm and nucleus in nonapoptotic cells" (2009). Open Access Articles. Paper 2207.