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Cytochrome c signalosome in mitochondria

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Abstract

Cytochrome c delicately tilts the balance between cell life (respiration) and cell death (apoptosis). Whereas cell life is governed by transient electron transfer interactions of cytochrome c inside the mitochondria, the cytoplasmic adducts of cytochrome c that lead to cell death are amazingly stable. Interestingly, the contacts of cytochrome c with its counterparts shift from the area surrounding the heme crevice for the redox complexes to the opposite molecule side when the electron flow is not necessary. The cytochrome c signalosome shows a higher level of regulation by post-translational modifications—nitration and phosphorylation—of the hemeprotein. Understanding protein interfaces, as well as protein modifications, would puzzle the mitochondrial cytochrome c-controlled pathways out and enable the design of novel drugs to silence the action of pro-survival and pro-apoptotic partners of cytochrome c.

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Abbreviations

Adx:

Adrenodoxin

AdxR:

NADPH-dependent adrenodoxin reductase

bc 1 :

Cytochrome bc 1 complex

CB:

Cytochrome binding

Cb 5 :

Cytochrome b 5

Cb 5R:

NADH-dependent cytochrome b 5 reductase

Cc :

Cytochrome c

Cc 552 :

Cytochrome c 552

CcO:

Cytochrome c oxidase

CcP:

Cytochrome c peroxidase

CH1:

Collagen homologous 1

CH2:

Collagen homologous 2

CL:

CardioLipin

ET:

Electron transfer

GALDH:

l-GAlactono-1,4-Lactone DeHydrogenase

IMM:

Inner mitochondrial membrane

IMS:

Intermembrane mitochondrial space

n-Cc :

Nitrated cytochrome c

NMR:

Nuclear magnetic resonance

OMM:

Outer mitochondrial membrane

p-Cc :

Phosphorylated cytochrome c

PCD:

Programmed cell death

PKCβ:

Protein kinase C β

PKCδ:

Protein kinase C δ

PRE:

Paramagnetic relaxation enhancement

PTB:

PhosphoTyrosine binding

R(N)OS:

Reactive (nitrogen)oxygen species

Sco:

Synthesis of cytochrome c oxidase

SH2:

Src homology 2

WT:

Wild-type

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Acknowledgments

The authors wish to thank Jonathan Martínez-Fábregas for helpful advice and critical reading of the manuscript. This work was funded by the Spanish Ministry of Science and Innovation (BFU2009-07190) and the Andalusian Government (BIO198 and P08-CVI-3876).

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  1. Instituto de Bioquímica Vegetal y Fotosíntesis, Centro de Investigaciones Científicas Isla de la Cartuja (cicCartuja), Universidad de Sevilla-CSIC, Avda. Américo Vespucio 49, 41092, Sevilla, Spain

    Irene Díaz-Moreno, José M. García-Heredia, Antonio Díaz-Quintana & Miguel A. De la Rosa

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  1. Irene Díaz-Moreno
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  2. José M. García-Heredia
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  3. Antonio Díaz-Quintana
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  4. Miguel A. De la Rosa
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Correspondence to Irene Díaz-Moreno or Miguel A. De la Rosa.

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Special Issue: Transient interactions in biology.

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Díaz-Moreno, I., García-Heredia, J.M., Díaz-Quintana, A. et al. Cytochrome c signalosome in mitochondria. Eur Biophys J 40, 1301–1315 (2011). https://doi.org/10.1007/s00249-011-0774-4

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