Oxidized or Reduced Cytochrome c and Axial Ligand Variants All Form the Apoptosome in Vitro

Biochemistry
Deanna L MendezRobert G Kranz

Abstract

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 Fe3+ heme) but not ferro (reduced, Fe2+ 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.

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Feb 16, 2017·Proceedings of the National Academy of Sciences of the United States of America·Deanna L MendezRobert G Kranz

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Citations

May 17, 2018·Cell Death and Differentiation·Loretta DorstynSharad Kumar
Nov 27, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Diego AraunaIván Palomo
May 18, 2021·Frontiers in Oncology·Yong XiaYoung Do Jung

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

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