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

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology; Department of Biochemistry and Molecular Pharmacology; Department of Cell Biology

Publication Date


Document Type



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.

DOI of Published Version



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

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

Related Resources

Link to Article in PubMed

PubMed ID