| Autor: |
Mendez DL; Department of Biology, Washington University in St. Louis , 1 Brookings Drive, St. Louis, Missouri 63130, United States., Akey IV; Department of Physiology and Biophysics, Boston University School of Medicine , 700 Albany Street, Boston, Massachusetts 02118, United States., Akey CW; Department of Physiology and Biophysics, Boston University School of Medicine , 700 Albany Street, Boston, Massachusetts 02118, United States., Kranz RG; Department of Biology, Washington University in St. Louis , 1 Brookings Drive, St. Louis, Missouri 63130, United States. |
| Abstrakt: |
Cytochrome c (cyt c) has two important roles in vertebrates: mitochondrial electron transport and activating the intrinsic cell death pathway (apoptosis). To initiate cell death, cyt c dissociates from the inner mitochondrial membrane and migrates to the cytosol. In the cytosol, cyt c interacts stoichiometrically with apoptotic protease activating factor 1 (Apaf-1) and upon ATP binding induces formation of the heptameric apoptosome. It is not clear however what the redox state of cyt c is when it functions as the "active signal" for apoptosis. Some reports have indicated that only ferri (i.e., oxidized Fe 3+ heme) but not ferro (reduced, Fe 2+ heme) cyt c forms the apoptosome. Facilitated by our recently described recombinant system for synthesizing novel human cyt c proteins, we use a panel of cyt c axial ligand variants that exhibit a broad range of redox potentials. These variants exist in different redox states. Here we show that cyt c wild type and cyt c H19M (reduced state) and cyt c M81A and cyt c M81H (oxidized state) all bind to Apaf-1 and form the apoptosome. |
