Physical contact between cytochrome c1 and cytochrome c increases the driving force for electron transfer

Pérez‐Mejías, Gonzalo; Olloqui‐Sariego, José Luis; Guerra‐Castellano, Alejandra; Díaz‐Quintana, Antonio; Calvente, Juan José; Andreu, Rafael; Rosa, Miguel Á. De la; Dı́az-Moreno, Irene

doi:10.1016/j.bbabio.2020.148277

Cited by 13 publications

(10 citation statements)

References 120 publications

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“…The interaction between Cc and its partners depends strongly on the ionic strength of the media, revealing the importance of charged residues such as lysines in its associations [33]. Lys8 and Lys53, with their side chains exposed to the solvent, are involved in the binding of Cc to most of its metabolic partners as they contribute to a positively charged Lys-rich patch at the hemeprotein surface [16,22,[34][35][36][37]. Since acetylation neutralizes the positive charge of lysines, this PTM might induce drastic changes in the physicochemical and structural features of Cc and could therefore alter interactions with its metabolic partners.…”

Section: Accepted Articlementioning

confidence: 99%

Structural and functional insights into lysine acetylation of cytochrome c using mimetic point mutants

et al. 2021

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Post-translational modifications frequently modulate protein functions. Lysine acetylation in particular plays a key role in interactions between respiratory cytochrome c and its metabolic partners. To date, in vivo acetylation of lysines at positions 8 and 53 has specifically been identified in mammalian cytochrome c, but little is known about the structural basis of acetylationinduced functional changes. Here, we independently replaced these two residues in recombinant human cytochrome c with glutamine to mimic lysine acetylation, and then characterized the structure and function of the resulting K8Q and K53Q mutants. We found that the physicochemical features were mostly unchanged in the two acetyl-mimetic mutants, but their thermal stability was significantly altered. Nuclear magnetic resonance chemical shift perturbations of the backbone amide resonances revealed local structural changes, and the thermodynamics and kinetics of electron transfer in mutants immobilized on gold electrodes showed an increase in both protein dynamics and solvent involvement in the redox process. We also observed that the K8Q (but not the K53Q) mutation slightly increased the binding affinity of cytochrome c to its physiological electron donor, cytochrome c 1 -which is a component of mitochondrial complex III, or cytochrome bc 1 -thus suggesting that Lys8 (but not Lys53) is located in the interaction area. Finally, the K8Q and K53Q mutants exhibited reduced efficiency as electron donors to complex IV, or cytochrome c oxidase.

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Section: Accepted Articlementioning

confidence: 99%

Structural and functional insights into lysine acetylation of cytochrome c using mimetic point mutants

et al. 2021

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“…C c competes with histones for binding to SET/TAF‐Iβ and NRP1, as inferred from 1D 1 H nuclear magnetic resonance (NMR) and electrophoretic mobility shift assays [31,132]. Furthermore, 2D [ 1 H‐ 15 N] NMR titration experiments revealed a spread pattern of residues on the C c surface affected by binding to histone chaperones, in particular residues at the haem‐surrounding area and the face opposite to the haem crevice [210–213]. Such experiments suggest that C c forms fuzzy complexes with histone chaperones, as reported in other systems [208].…”

Section: Acidic Regions As Main Targets For Cytochrome Cmentioning

confidence: 99%

Mitochondrial cytochrome c shot towards histone chaperone condensates in the nucleus

et al. 2021

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Despite mitochondria being key for the control of cell homeostasis and fate, their role in DNA damage response (DDR) is usually just regarded as an apoptotic trigger. However, growing evidence points to mitochondrial factors modulating nuclear functions. Remarkably, after DNA damage, cytochrome c (Cc) interacts in the cell nucleus with a variety of well-known histone chaperones, whose activity is competitively inhibited by the hemeprotein. As nuclear Cc inhibits the nucleosome assembly/disassembly activity of histone chaperones, it might indeed affect chromatin dynamics and histone deposition on DNA. Several histone chaperones actually interact with Cc Lys residues through their acidic regions, which are also involved in heterotypic interactions leading to liquid-liquid phase transitions responsible for the assembly of nuclear condensates, including heterochromatin. This relies on dynamic histone-DNA interactions that can be modulated by acetylation of specific histone Lys residues.Thus, Cc may have a major regulatory role in DNA repair by fine-tuning nucleosome assembly activity and likely nuclear condensate formation.

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“…It also seems to increase the local concentration of C c available near the proximal site, allowing a rapid turnover of C c molecules [ 8 , 9 ]. Recently, the molecular basis of electron transfer from C c 1 in CIII to C c has been described [ 10 , 11 ]. According to the data, the coupling of redox potential shifts the conformational cycle of the Rieske subunit and the binding of C c to C c 1 causes electrons to flow in a single direction [ 11 ].…”

Section: The Pleiotropic Role Of Cytochrome C Imentioning

confidence: 99%

“…Recently, the molecular basis of electron transfer from C c 1 in CIII to C c has been described [ 10 , 11 ]. According to the data, the coupling of redox potential shifts the conformational cycle of the Rieske subunit and the binding of C c to C c 1 causes electrons to flow in a single direction [ 11 ]. C c has other redox functions, acting as a reactive oxygen species (ROS) scavenger and participating in the import of redox-coupled cysteine-rich proteins via Erv1-Mia40 [ 12 , 13 , 14 ].…”

Section: The Pleiotropic Role Of Cytochrome C Imentioning

confidence: 99%

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Post-Translational Modifications of Cytochrome c in Cell Life and Disease

Guerra‐Castellano

Márquez

Pérez‐Mejías

et al. 2020

IJMS

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Mitochondria are the powerhouses of the cell, whilst their malfunction is related to several human pathologies, including neurodegenerative diseases, cardiovascular diseases, and various types of cancer. In mitochondrial metabolism, cytochrome c is a small soluble heme protein that acts as an essential redox carrier in the respiratory electron transport chain. However, cytochrome c is likewise an essential protein in the cytoplasm acting as an activator of programmed cell death. Such a dual role of cytochrome c in cell life and death is indeed fine-regulated by a wide variety of protein post-translational modifications. In this work, we show how these modifications can alter cytochrome c structure and functionality, thus emerging as a control mechanism of cell metabolism but also as a key element in development and prevention of pathologies.

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Physical contact between cytochrome c1 and cytochrome c increases the driving force for electron transfer

Cited by 13 publications

References 120 publications

Structural and functional insights into lysine acetylation of cytochrome c using mimetic point mutants

Structural and functional insights into lysine acetylation of cytochrome c using mimetic point mutants

Mitochondrial cytochrome c shot towards histone chaperone condensates in the nucleus

Post-Translational Modifications of Cytochrome c in Cell Life and Disease

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