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

2009; National Academy of Sciences; Volume: 106; Issue: 8 Linguagem: Inglês

10.1073/pnas.0809279106

1091-6490

Luiz C. Godoy, Cristina Muñoz‐Pinedo, Laura Castro, Simone Cardaci, Christopher M. Schonhoff, Michael R. King, Verónica Tórtora, Mónica Marı́n, Qian Miao, Jian Jiang, Alexandr A. Kapralov, Ronald Jemmerson, Gary Silkstone, Jinal N. Patel, James Evans, Michael T. Wilson, Douglas R. Green, Valerian E. Kagan, Rafael Radí, Joan B. Mannick,

ATP Synthase and ATPases Research

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.