Phosphorylation of cytochrome c at tyrosine 48 finely regulates its binding to the histone chaperone SET/TAF-Iβ in the nucleus.

Post-translational modifications (PTMs) of proteins are ubiquitous processes present in all life kingdoms, involved in the regulation of protein stability, subcellular location and activity. In this context, cytochrome c (Cc) is an excellent case study to analyze the structural and functional changes induced by PTMS as Cc is a small, moonlighting protein playing different roles in different cell compartments at different cell-cycle stages. Cc is actually a key component of the mitochondrial electron transport chain (ETC) under homeostatic conditions but is translocated to the cytoplasm and even the nucleus under apoptotic conditions and/or DNA damage.

Cytochrome prompts the recruitment of its nuclear partners SET/TAF-Iβ and NPM1 into biomolecular condensates.

Compartmentalization of proteins by liquid-liquid phase separation (LLPS) is used by cells to control biochemical reactions spatially and temporally. Among them, the recruitment of proteins to DNA foci and nucleolar trafficking occur by biomolecular condensation. Within this frame, the oncoprotein SET/TAF-Iβ plays a key role in both chromatin remodeling and DNA damage response, as does nucleophosmin (NPM1) which indeed participates in nucleolar ribosome synthesis.

Phosphorylation at the disordered N-end makes HuR accumulate and dimerize in the cytoplasm.

Human antigen R (HuR) is an RNA binding protein mainly involved in maintaining the stability and controlling the translation of mRNAs, critical for immune response, cell survival, proliferation and apoptosis. Although HuR is a nuclear protein, its mRNA translational-related function occurs at the cytoplasm, where the oligomeric form of HuR is more abundant. However, the regulation of nucleo-cytoplasmic transport of HuR and its connection with protein oligomerization remain unclear.

Serving the scientific community: FEBS Open Bio in 2024.

FEBS Open Bio is committed to not only publishing sound science but also to supporting early-career researchers and the scientific community as a whole. In this editorial, we look back at how the journal recognised and rewarded excellent research in 2023 and look forward to 2024.

Cytochrome c lysine acetylation regulates cellular respiration and cell death in ischemic skeletal muscle.

Skeletal muscle is more resilient to ischemia-reperfusion injury than other organs. Tissue specific post-translational modifications of cytochrome c (Cytc) are involved in ischemia-reperfusion injury by regulating mitochondrial respiration and apoptosis. Here, we describe an acetylation site of Cytc, lysine 39 (K39), which was mapped in ischemic porcine skeletal muscle and removed by sirtuin5 in vitro.

Innovation and renovation: FEBS Open Bio in 2023.

FEBS Open Bio is constantly evolving to best suit the needs of the scientific community. In this Editorial, we review the various new initiatives introduced in 2022 and look forward to the opportunities and challenges that lie ahead in 2023.

Ensuring image integrity in the digital age.

FEBS Open Bio and our fellow FEBS Press journals have a strong commitment to maintaining the integrity of the scientific literature. The life sciences, in particular, are suffering from an ongoing reproducibility crisis, and this may in part be fuelled by mistakes, manipulation or outright fabrication of the presented data. We were recently made aware of several articles published in FEBS Open Bio that appear to contain full or partial duplications of images from other published articles in a different scientific context.

Phosphorylation disrupts long-distance electron transport in cytochrome c.

It has been recently shown that electron transfer between mitochondrial cytochrome c and the cytochrome c subunit of the cytochrome bc can proceed at long-distance through the aqueous solution. Cytochrome c is thought to adjust its activity by changing the affinity for its partners via Tyr48 phosphorylation, but it is unknown how it impacts the nanoscopic environment, interaction forces, and long-range electron transfer. Here, we constrain the orientation and separation between cytochrome c and cytochrome c or the phosphomimetic Y48pCMF cytochrome c, and deploy an array of single-molecule, bulk, and computational methods to investigate the molecular mechanism of electron transfer regulation by cytochrome c phosphorylation.

Nucleus-translocated mitochondrial cytochrome c liberates nucleophosmin-sequestered ARF tumor suppressor by changing nucleolar liquid-liquid phase separation.

The regular functioning of the nucleolus and nucleus-mitochondria crosstalk are considered unrelated processes, yet cytochrome c (Cc) migrates to the nucleus and even the nucleolus under stress conditions. Nucleolar liquid-liquid phase separation usually serves the cell as a fast, smart mechanism to control the spatial localization and trafficking of nuclear proteins. Actually, the alternative reading frame (ARF), a tumor suppressor protein sequestered by nucleophosmin (NPM) in the nucleoli, is shifted out from NPM upon DNA damage.

PP2A is activated by cytochrome upon formation of a diffuse encounter complex with SET/TAF-Iβ.

Intrinsic protein flexibility is of overwhelming relevance for intermolecular recognition and adaptability of highly dynamic ensemble of complexes, and the phenomenon is essential for the understanding of numerous biological processes. These conformational ensembles-encounter complexes-lack a unique organization, which prevents the determination of well-defined high resolution structures. This is the case for complexes involving the oncoprotein SET/template-activating factor-Iβ (SET/TAF-Iβ), a histone chaperone whose functions and interactions are significantly affected by its intrinsic structural plasticity.

Electric field-induced functional changes in electrode-immobilized mutant species of human cytochrome c.

Post-translational modifications and naturally occurring mutations of cytochrome c have been recognized as a regulatory mechanism to control its biology. In this work, we investigate the effect of such in vivo chemical modifications of human cytochrome c on its redox properties in the adsorbed state onto an electrode. In particular, tyrosines 48 and 97 have been replaced by the non-canonical amino acid p-carboxymethyl-L-phenylalanine (pCMF), thus mimicking tyrosine phosphorylation.

Entering the second decade: FEBS Open Bio in 2022.

FEBS Open Bio continues to go from strength to strength, with 2021 perhaps marking its most exciting year. In this Editorial, the Editor-in-Chief Miguel A. De la Rosa looks back at all the new developments of 2021 and forecasts the outlook for 2022.

FEBS Open Bio: past, present and future.

In celebration of the 10th anniversary of FEBS Open Bio, we spoke to some of the key figures of the journal's genesis, development, and its future direction, and recount here their thoughts and experiences. Prof. Félix.

Ten years of FEBS Open Bio.

This month, FEBS Open Bio celebrates its 10th birthday. To celebrate the journal's first decade, we present this special anniversary issue, comprised of editorials, reviews, and research articles especially commissioned for the occasion. In this introductory editorial, we invite the reader to join us as we reminisce over the journal's past, celebrate its present, and look forward to its future.

Membraneless organelles: a smart design for metabolic control.

While most organelles are surrounded by membranes, cells also contain membraneless organelles, which remain separated in the cell by avoiding the mixture of their components with the surroundings. Actually, liquid-liquid phase separation provides a simple but smart mechanism for the cell to control the spatial localization and processing of molecules, without relying on membrane boundaries. This Special 'In the Limelight' section, entitled 'Membraneless organelles', consists of three review articles, each focused on a particular aspect.

Post-translational Control of RNA-Binding Proteins and Disease-Related Dysregulation.

Cell signaling mechanisms modulate gene expression in response to internal and external stimuli. Cellular adaptation requires a precise and coordinated regulation of the transcription and translation processes. The post-transcriptional control of mRNA metabolism is mediated by the so-called RNA-binding proteins (RBPs), which assemble with specific transcripts forming messenger ribonucleoprotein particles of highly dynamic composition.

Mitochondrial cytochrome c shot towards histone chaperone condensates in the nucleus.

Despite mitochondria being key for the control of cell homeostasis and fate, their role in DNA damage response 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 haem protein.

Inhibition of the PP2A activity by the histone chaperone ANP32B is long-range allosterically regulated by respiratory cytochrome c.

Repair of injured DNA relies on nucleosome dismantling by histone chaperones and de-phosphorylation events carried out by Protein Phosphatase 2A (PP2A). Typical histone chaperones are the Acidic leucine-rich Nuclear Phosphoprotein 32 family (ANP32) members, e.g.

IUBMB focused meeting/FEBS workshop: Crosstalk between nucleus and mitochondria in human disease (CrossMitoNus).

The IUBMB Focused Meeting/FEBS Workshop titled 'Crosstalk between Nucleus and Mitochondria in Human Disease'(CrossMitoNus) will take place on September 7-10, 2021 in Seville (Spain), with the support of both the International Union of Biochemistry and Molecular Biology (IUBMB) and the Federation of European Biochemical Societies (FEBS). Mitochondria are key organelles that act as a hub for vital metabolic processes, for example, energy transduction by oxidative phosphorylation, intermediary metabolism, redox signaling, calcium and iron homeostasis, heme and steroid biosynthesis, metal homeostasis, programmed cell death, and innate immunity. Consequently, a wide assortment of diseases-including neurodegenerative disorders, diabetes, cancer, rare syndromes, and many others-relate to mitochondrial dysfunction.

Proposed mechanism for regulation of H O -induced programmed cell death in plants by binding of cytochrome c to 14-3-3 proteins.

Programmed cell death (PCD) is crucial for development and homeostasis of all multicellular organisms. In human cells, the double role of extra-mitochondrial cytochrome c in triggering apoptosis and inhibiting survival pathways is well reported. In plants, however, the specific role of cytochrome c upon release from the mitochondria remains in part veiled yet death stimuli do trigger cytochrome c translocation as well.

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

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 is a small soluble heme protein that acts as an essential redox carrier in the respiratory electron transport chain. However, cytochrome is likewise an essential protein in the cytoplasm acting as an activator of programmed cell death.

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

In oxidative phosphorylation, the transfer of electrons from reduced cofactors to molecular oxygen via the electron transport chain (ETC) sustains the electrochemical transmembrane potential needed for ATP synthesis. A key component of the ETC is complex III (CIII, cytochrome bc), which transfers electrons from reduced ubiquinone to soluble cytochrome c (Cc) coupled to proton translocation into the mitochondrial intermembrane space. One electron from every two donated by hydroquinone at site P is transferred to Cc via the Rieske-cytochrome c (Cc) pathway.

Wheel and Deal in the Mitochondrial Inner Membranes: The Tale of Cytochrome and Cardiolipin.

Cardiolipin oxidation and degradation by different factors under severe cell stress serve as a trigger for genetically encoded cell death programs. In this context, the interplay between cardiolipin and another mitochondrial factor-cytochrome -is a key process in the early stages of apoptosis, and it is a matter of intense research. Cytochrome interacts with lipid membranes by electrostatic interactions, hydrogen bonds, and hydrophobic effects.

A warm welcome to our new editors.

In this Editorial, the Editor-in-Chief Professor Miguel A. De la Rosa introduces the new members of the Editorial Board and discusses the effects of COVID-19 on the journal.