Telencephalon ‐specific Alkbh1 conditional knockout mice display hippocampal atrophy and impaired learning
AbstractAlkB homolog 1 (ALKBH1) is responsible for the biogenesis of 5 ‐formylcytidine (f5C) on mitochondrial tRNAMet and essential for mitochondrial protein synthesis. The brain, especially the hippocampus, is highly susceptible to mitochondrial dysfunction; hence, the maintenance of mitochondrial activity is strongly required to prevent disorders associated with hippocampal malfunction. To study the role of ALKBH1 in the hippocampus, we generated dorsal telencephalon ‐specificAlkbh1 conditional KO (cKO) mice in inbred C57BL/6 background. These mice showed reduced activity of the respiratory chain complex, hippocampal...
Source: FEBS Letters - May 4, 2021 Category: Biochemistry Authors: Layla Kawarada, Masahiro Fukaya, Ryo Saito, Hidetoshi Kassai, Hiroyuki Sakagami, Atsu Aiba Tags: RESEARCH LETTER Source Type: research

MXD/MIZ1 transcription regulatory complexes activate the expression of Myc ‐repressed genes
We report that MXDs activate transcription ofp15 andp21 in U2OS cells. This activation required DNA binding by MXDs and their interaction with MIZ1. MXD mutants deficient in MIZ1 ‐binding interacted with the Myc‐binding partner MAX and were active as repressors of MYC‐activated genes but failed to activate MYC‐repressed genes. Mutant MXDs with reduced DNA binding affinity interacted with MAX and MIZ1 but neither repressed nor activated transcription. Our data show th at MXDs and MYC have a reciprocally antagonistic potential to regulate transcription of target genes. (Source: FEBS Letters)
Source: FEBS Letters - April 29, 2021 Category: Biochemistry Authors: Anton Shostak, G éza Schermann, Axel Diernfellner, Michael Brunner Tags: RESEARCH ARTICLE Source Type: research

K160 in the RNA ‐binding domain of the orf virus virulence factor OV20.0 is critical for its functions in counteracting host antiviral defense
AbstractThe OV20.0 virulence factor of orf virus (ORFV) antagonizes host antiviral responses. One mechanism through which it functions is by inhibiting activation of the dsRNA ‐activated protein kinase R (PKR) by sequestering dsRNA and by physically interacting with PKR. Sequence alignment indicated that several key residues critical for dsRNA‐binding were conserved in OV20.0, and their contribution to OV20.O function was investigated in this study. We found that resi dues F141, K160, R164 were responsible for the dsRNA‐binding ability of OV20.0. Interestingly, mutation at K160 (K160A) diminished the OV20.0–PKR...
Source: FEBS Letters - April 28, 2021 Category: Biochemistry Authors: Guan ‐Ru Liao, Yeu‐Yang Tseng, Ching‐Yu Tseng, Ying‐Ping Huang, Ching‐Hsiu Tsai, Hao‐Ping Liu, Wei‐Li Hsu Tags: RESEARCH ARTICLE Source Type: research

MICOS and the mitochondrial inner membrane morphology – when things get out of shape
Mitochondria play a key role in cellular signalling, metabolism and energetics. Proper architecture and remodelling of the inner mitochondrial membrane are essential for efficient respiration, apoptosis and quality control in the cell. Several protein complexes including mitochondrial contact site and cristae organizing system (MICOS), F1FO‐ATP synthase, and Optic Atrophy 1 (OPA1), facilitate formation, maintenance and stability of cristae membranes. MICOS, the F1FO‐ATP synthase, OPA1 and inner membrane phospholipids such as cardiolipin and phosphatidylethanolamine interact with each other to organize the inner membran...
Source: FEBS Letters - April 28, 2021 Category: Biochemistry Authors: Indrani Mukherjee, Mausumi Ghosh, Michael Meinecke Tags: Review Article Source Type: research

Front Cover
Cover illustration 3D representation of a mitochondrion. Image credit: wir0man. (Source: FEBS Letters)
Source: FEBS Letters - April 28, 2021 Category: Biochemistry Tags: Issue Information Source Type: research

Molecular bases of mitochondrial disorders
(Source: FEBS Letters)
Source: FEBS Letters - April 28, 2021 Category: Biochemistry Authors: Agnieszka Chacinska, Peter Rehling Tags: Editorial Source Type: research

MICOS and the mitochondrial inner membrane morphology – when things get out of shape
Mitochondria play a key role in cellular signalling, metabolism and energetics. Proper architecture and remodelling of the inner mitochondrial membrane are essential for efficient respiration, apoptosis and quality control in the cell. Several protein complexes including mitochondrial contact site and cristae organizing system (MICOS), F1FO‐ATP synthase, and Optic Atrophy 1 (OPA1), facilitate formation, maintenance and stability of cristae membranes. MICOS, the F1FO‐ATP synthase, OPA1 and inner membrane phospholipids such as cardiolipin and phosphatidylethanolamine interact with each other to organize the inner membran...
Source: FEBS Letters - April 28, 2021 Category: Biochemistry Authors: Indrani Mukherjee, Mausumi Ghosh, Michael Meinecke Tags: Review Article Source Type: research

Front Cover
Cover illustration 3D representation of a mitochondrion. Image credit: wir0man. (Source: FEBS Letters)
Source: FEBS Letters - April 28, 2021 Category: Biochemistry Tags: Issue Information Source Type: research

Molecular bases of mitochondrial disorders
(Source: FEBS Letters)
Source: FEBS Letters - April 28, 2021 Category: Biochemistry Authors: Agnieszka Chacinska, Peter Rehling Tags: Editorial Source Type: research

Gene network analysis using SWIM reveals interplay between the transcription factor ‐encoding genes HMGA1, FOXM1, and MYBL2 in triple‐negative breast cancer
Among breast cancer subtypes, triple ‐negative breast cancer (TNBC) is the most aggressive with the worst prognosis and the highest rates of metastatic disease. To identify TNBC gene signatures, we applied the network‐based methodology implemented by the SWIM software to gene expression data of TNBC patients in The Cancer Genome At las (TCGA) database. SWIM enables to predict key (switch) genes within the co‐expression network, whose perturbations in expression pattern and abundance may contribute to the (patho)biological phenotype. Here, SWIM analysis revealed an interesting interplay between the genes encoding the ...
Source: FEBS Letters - April 27, 2021 Category: Biochemistry Authors: Giulia Fiscon, Silvia Pegoraro, Federica Conte, Guidalberto Manfioletti, Paola Paci, Qinghua Cui Tags: Research Article Source Type: research

Copper binding and reactivity at the histidine brace motif: insights from mutational analysis of the Pseudomonas fluorescens copper chaperone CopC
AbstractThe histidine brace (His ‐brace) is a copper‐binding motif that is associated with both oxidative enzymes and proteinaceous copper chaperones. Here, we used biochemical and structural methods to characterize mutants of a His‐brace‐containing copper chaperone from Pseudomonas fluorescens (PfCopC). A total of 15 amino acid variants in primary and second sphere residues were produced and characterised in terms of their copper‐binding and redox properties. PfCopC has a very high affinity for Cu(II) and also binds Cu(I). A high reorganisation barrier likely prevents redox‐cycling and, thus, catalys...
Source: FEBS Letters - April 25, 2021 Category: Biochemistry Authors: Johan Ø. Ipsen, Cristina Hernández‐Rollán, Sebastian J. Muderspach, Søren Brander, Andreas B. Bertelsen, Poul Erik Jensen, Morten H.H. Nørholm, Leila Lo Leggio, Katja S. Johansen Tags: RESEARCH ARTICLE Source Type: research

Human SND2 mediates ER targeting of GPI ‐anchored proteins with low hydrophobic GPI attachment signals
Over 100 glycosylphosphatidylinositol ‐anchored proteins (GPI‐APs) are encoded in the mammalian genome. It is not well understood how these proteins are targeted and translocated to the endoplasmic reticulum (ER). Here, we reveal that many GPI‐APs, such as CD59, CD55, and CD109, utilize human SND2 (hSND2)‐dependent ER targeting machinery. We also found that signal recognition particle receptors seem to cooperate with hSND2 to target GPI‐APs to the ER. Both the N‐terminal signal sequence and C‐terminal GPI attachment signal of GPI‐APs contribute to ER targetingvia the hSND2 ‐dependent pathway. Particularly...
Source: FEBS Letters - April 24, 2021 Category: Biochemistry Authors: Jing Yang, Tetsuya Hirata, Yi ‐Shi Liu, Xin‐Yu Guo, Xiao‐Dong Gao, Taroh Kinoshita, Morihisa Fujita, Sandro Sonnino Tags: Research Article Source Type: research

Endothelial cell autophagy in homeostasis and cancer
Autophagy, the major lysosomal pathway for the degradation and recycling of cytoplasmic materials, is increasingly recognized as a major player in endothelial cell (EC) biology and vascular pathology. Particularly in solid tumors, tumor microenvironmental stress such as hypoxia, nutrient deprivation, inflammatory mediators, and metabolic aberrations stimulates autophagy in tumor ‐associated blood vessels. Increased autophagy in ECs may serve as a mechanism to alleviate stress and restrict exacerbated inflammatory responses. However, increased autophagy in tumor‐associated ECs can re‐model metabolic pathways and affec...
Source: FEBS Letters - April 24, 2021 Category: Biochemistry Authors: Jelle Verhoeven, Jef Baelen, Madhur Agrawal, Patrizia Agostinis, Hitoshi Nakatogawa Tags: Review Source Type: research

α‐Syntrophin alleviates ER stress to maintain protein homeostasis during myoblast differentiation
In this study, we focused on abnormal myotube formation of the α‐syntrophin knockdown C2 cell line (SNKD). The overall amount of intracellular protein and muscle‐specific proteins in SNKD cells were significantly lower than th ose in the control. Akt‐mTOR signaling, an important pathway for protein synthesis and muscle hypertrophy, was downregulated. In addition, the levels of endoplasmic reticulum (ER) stress markers increased in SNKD cells. The decrease in intracellular protein synthesis and reduction in the myotube d iameter in SNKD cells were restored by 4‐phenylbutyric acid, a chemical chaperone, or over...
Source: FEBS Letters - April 22, 2021 Category: Biochemistry Authors: Jae Yun Moon, Hye Sun Kim, Lukas Alfons Huber Tags: Research Article Source Type: research

Resveratrol reduces cardiac NLRP3 ‐inflammasome activation and systemic inflammation to lessen doxorubicin‐induced cardiotoxicity in juvenile mice
AbstractDoxorubicin is a very effective anticancer agent that is widely used in pediatric cancer patients. Nevertheless, doxorubicin is known to have cardiotoxic effects that may progress to cardiomyopathy later in life. We have recently shown that co ‐treatment of resveratrol with doxorubicin in juvenile mice attenuates late‐onset hypertension‐induced cardiomyopathy. However, the molecular mechanism responsible for these changes remains unknown. Herein, we show that the cardiac NLRP3 inflammasome plays a crucial role in regulating cardiac injury in a doxorubicin‐treated juvenile mouse model and the detrimental eff...
Source: FEBS Letters - April 20, 2021 Category: Biochemistry Authors: Zaid H. Maayah, Abrar S. Alam, Shingo Takahara, Shubham Soni, Mourad Ferdaoussi, Nobutoshi Matsumura, Beshay N. Zordoky, David D. Eisenstat, Jason R.B. Dyck Tags: COMMUNICATION Source Type: research

Retraction statement: MicroRNA ‐222 promotes tumorigenesis via targeting DKK2 and activating the Wnt/β‐catenin signaling pathway
https://doi.org/10.1016/j.febslet.2013.04.002The above article fromFEBS Letters by Qifeng Li, Ke Shen, Yang Zhao, Xiaoguang He, Chenkai Ma, Lin Wang, Baocheng Wang, Jianwen Liu, Jie Ma, published online on 12 April 2013, in Wiley Online Library (https://doi.org/10.1016/j.febslet.2013.04.002), has been retracted by agreement between the authors, the journal Managing Editor, Felix Wieland, and John Wiley& Sons. The retraction has been agreed due to the identification of duplications in Figures 1D, 3B, and 4A –C. The authors were unable to provide the raw data underlying these figure panels. As a result, the journal...
Source: FEBS Letters - April 20, 2021 Category: Biochemistry Tags: Retraction Source Type: research

Corrigendum
(Source: FEBS Letters)
Source: FEBS Letters - April 12, 2021 Category: Biochemistry Tags: Corrigendum Source Type: research

Front Cover
Cover illustration The cover image refers to the article “Sharing biological data: why, when, and how” by S.L. Wilsonet al. (pp. 847 –863). (Source: FEBS Letters)
Source: FEBS Letters - April 12, 2021 Category: Biochemistry Tags: Issue Information Source Type: research

Sharing biological data: why, when, and how
(Source: FEBS Letters)
Source: FEBS Letters - April 12, 2021 Category: Biochemistry Authors: Samantha L. Wilson, Gregory P. Way, Wout Bittremieux, Jean ‐Paul Armache, Melissa A. Haendel, Michael M. Hoffman Tags: The Scientists' Forum Source Type: research

Corrigendum
(Source: FEBS Letters)
Source: FEBS Letters - April 11, 2021 Category: Biochemistry Tags: Corrigendum Source Type: research

Front Cover
Cover illustration The cover image refers to the article “Sharing biological data: why, when, and how” by S.L. Wilsonet al. (pp. 847 –863). (Source: FEBS Letters)
Source: FEBS Letters - April 11, 2021 Category: Biochemistry Tags: Issue Information Source Type: research

Sharing biological data: why, when, and how
(Source: FEBS Letters)
Source: FEBS Letters - April 11, 2021 Category: Biochemistry Authors: Samantha L. Wilson, Gregory P. Way, Wout Bittremieux, Jean ‐Paul Armache, Melissa A. Haendel, Michael M. Hoffman Tags: The Scientists' Forum Source Type: research

Activation probability of a single na ïve T cell upon TCR ligation is controlled by T cells interacting with the same antigen‐presenting cell
AbstractAccurate recognition of antigens by specific T cells is crucial for adaptive immunity to work properly. The activation of a T cell antigen ‐specific response by an antigen presenting cell (APC) has not been clearly measured at a single T cell level. It is also unknown whether the cell extrinsic environment alters antigen recognition by a T cell. To measure the activation probability of a single T cell by an APC, we performed a single cell live imaging assay and found that the activation probability changes depending not only on the antigens but also on the interactions of other T cells with the APC. We found that...
Source: FEBS Letters - April 8, 2021 Category: Biochemistry Authors: Hiroaki Machiyama, Tomoyuki Yamaguchi, Tomonobu M Watanabe, Toshio Yanagida, Hideaki Fujita Tags: RESEARCH LETTER Source Type: research

Mitochondrial dynamics in health and disease
In animals, mitochondria are mainly organised into an interconnected tubular network extending across the cell along a cytoskeletal scaffold. Mitochondrial fission and fusion, as well as distribution along cytoskeletal tracks, are counterbalancing mechanisms acting in concert to maintain a mitochondrial network tuned to cellular function. Balanced mitochondrial dynamics permits quality control of the network including biogenesis and turnover, and distribution of mitochondrial DNA, and is linked to metabolic status. Cellular and organismal health relies on a delicate balance between fission and fusion, and large rearrangeme...
Source: FEBS Letters - April 5, 2021 Category: Biochemistry Authors: Nethmi M.B. Yapa, Valerie Lisnyak, Boris Reljic, Michael T. Ryan, Peter Rehling Tags: Review Article Source Type: research

Calcium transfer between endoplasmic reticulum and mitochondria in liver diseases
Calcium (Ca2+) is a second messenger essential for cellular homeostasis. Inside the cell, Ca2+ is compartmentalized and exchanged among organelles in response to both external and internal stimuli. Mitochondria ‐associated membranes (MAMs) provide a platform for proteins and channels involved in Ca2+ transfer between the endoplasmic reticulum (ER) and mitochondria. Deregulated Ca2+ signaling and proteins regulating ER –mitochondria interactions have been linked to liver diseases and intensively investigated in recent years. In this review, we summarize the role of MAM‐resident proteins in Ca2+ transfer and their ...
Source: FEBS Letters - April 4, 2021 Category: Biochemistry Authors: Chaonan Jin, Pavitra Kumar, Jordi Gracia ‐Sancho, Jean‐François Dufour, Felix Wieland Tags: Review Article Source Type: research

Enhanced binding of the N501Y ‐mutated SARS‐CoV‐2 spike protein to the human ACE2 receptor: insights from molecular dynamics simulations
Recently, severe acute respiratory syndrome coronavirus 2 (SARS ‐CoV‐2) variants (B.1.1.7 and B.1351) have emerged harbouring mutations that make them highly contagious. The N501Y mutation within the receptor‐binding domain (RBD) of the spike protein of these SARS‐CoV‐2 variants may enhance binding to the human angiotensin‐converting enzyme 2 (hACE2) . However, no molecular explanation for such an enhanced affinity has so far been provided. Here, using all‐atom molecular dynamics simulations, we show that Y501 in the mutated RBD can be well‐coordinated by Y41 and K353 in hACE2 through hydrophobic interactio...
Source: FEBS Letters - April 3, 2021 Category: Biochemistry Authors: Binquan Luan, Haoran Wang, Tien Huynh, Michael Bubb Tags: Research Letter Source Type: research

Extracellular vesicles and intercellular communication in the central nervous system
Neurons and glial cells of the central nervous system (CNS) release extracellular vesicles (EVs) to the interstitial fluid of the brain and spinal cord parenchyma. EVs contain proteins, nucleic acids and lipids that can be taken up by, and modulate the behaviour of, neighbouring recipient cells. The functions of EVs have been extensively studied in the context of neurodegenerative diseases. However, mechanisms involved in EV ‐mediated neuron–glial communication under physiological conditions or healthy ageing remain unclear. A better understanding of the myriad roles of EVs in CNS homeostasis is essential for the d...
Source: FEBS Letters - April 3, 2021 Category: Biochemistry Authors: Lorena R. Lizarraga ‐Valderrama, Graham K. Sheridan Tags: Review Article Source Type: research

Structural features of the plant N ‐recognin ClpS1 and sequence determinants in its targets that govern substrate selection
AbstractIn the N ‐degron pathway of protein degradation ofEscherichia coli, the N ‐recognin ClpS identifies substrates bearing N‐terminal phenylalanine, tyrosine, tryptophan, or leucine and delivers them to the Clp protease. Chloroplasts contain the Clp system, but whether chloroplastic ClpS1 adheres to the same constraints is unknown. Moreover, the structural underpinnings o f substrate recognition are not completely defined. We show that ClpS1 recognizes canonical residues of theE. coli N ‐degron pathway. The residue in second position influences recognition (especially in N‐terminal ends starting with leucine)...
Source: FEBS Letters - April 1, 2021 Category: Biochemistry Authors: Dianela Aguilar Lucero, Alejo Cantoia, Carolina S ánchez‐López, Andrés Binolfi, Axel Mogk, Eduardo A. Ceccarelli, Germán L. Rosano Tags: RESEARCH LETTER Source Type: research

Porphyromonas gingivalis enhances pneumococcal adhesion to human alveolar epithelial cells by increasing expression of host platelet ‐activating factor receptor
AbstractStreptococcus pneumoniae causes pneumonia by infecting the alveolar epithelium via binding to host receptors, such as the platelet ‐activating factor receptor (PAFR). Although chronic periodontitis has been identified as a pneumonia risk factor, how periodontopathic bacteria cause pneumonia is not known. We found thatS. pneumoniae adhered to PAFR expressed on A549 human alveolar epithelial cells stimulated byPorphyromonas gingivalis culture supernatant, and this was abrogated by a PAFR ‐specific inhibitor. Among the major virulence factors ofP. gingivalis (lipopolysaccharide, fimbriae and gingipains [Rgps and K...
Source: FEBS Letters - April 1, 2021 Category: Biochemistry Authors: Noriaki Kamio, Mayumi Hayata, Muneaki Tamura, Hajime Tanaka, Kenichi Imai Tags: RESEARCH LETTER Source Type: research

Generation and characterization of a high ‐affinity chimeric anti‐OX40 antibody with potent anti‐tumor activity
AbstractOX40 is a costimulatory molecule that belongs to the tumor necrosis factor receptor (TNFR) superfamily. OX40 agonist ‐based combinations are emerging as promising candidates for novel cancer immunotherapy. Clinical trials have shown that OX40 agonist antibodies could lead to better results in cancer patients. Using a hybridoma platform and three different types of immunization strategies, namely recombinant prot ein, DNA, and overexpressing cells, we identified a chimeric anti‐OX40 antibody (mAb035‐hIgG1 from DNA immunization) that shows excellent binding specificity, and slightly stronger activation of human...
Source: FEBS Letters - April 1, 2021 Category: Biochemistry Authors: Yongli Yang, Xiaojuan Chai, Wenfang Xin, Dongxu Wang, Chaohui Dai, Feng Qian, Teddy Yang Tags: RESEARCH ARTICLE Source Type: research

The circadian rhythm regulator RpaA modulates photosynthetic electron transport and alters the preferable temperature range for growth in a cyanobacterium
In this study, we detected a PTRG upshift in a mutant strain ofSynechococcus  elongatus PCC 7942 lacking the circadian rhythm regulator RpaA. Subsequent analyses revealed that RpaA decreases the electron transport from photosystem I to NADPH. The change in electron transport likely inhibits H2O2 generation under high ‐temperature conditions and contributes to the observed PTRG upshift inrpaA‐deficient cells. The importance of the effects of the circadian rhythm regulator on the PTRG is discussed. (Source: FEBS Letters)
Source: FEBS Letters - March 31, 2021 Category: Biochemistry Authors: Hazuki Hasegawa, Tatsuhiro Tsurumaki, Sousuke Imamura, Kintake Sonoike, Kan Tanaka, Peter Brzezinski Tags: Research Letter Source Type: research

The CDC37 ‐HSP90 chaperone complex co‐translationally degrades the nascent kinase‐dead mutant of HIPK2
ABSTRACTHomeodomain ‐interacting protein kinase 2 (HIPK2) is a highly conserved, constitutively active Ser/Thr protein kinase that is involved in various important biological processes. HIPK2 activates itself by auto‐phosphorylation during its synthesis, and its activity is mainly controlled through modulation of i ts expression by ubiquitin‐dependent degradation. By comparing the expression of wild‐type and kinase‐defective HIPK2, we have recently described a novel mechanism of HIPK2 regulation that is based on preferential co‐translational degradation of kinase‐defective versus wild‐type HIPK2. H ere, we ...
Source: FEBS Letters - March 31, 2021 Category: Biochemistry Authors: Jan Paul M üller, Karl‐Heinz Klempnauer Tags: RESEARCH LETTER Source Type: research

Front Cover
Cover illustration The cover image refers to the article “Structures of ABC transporters: handle with care” where Lewinson, Orelle and Seeger advocate that the mechanistic interpretation of structures of ABC transporters is not trivial and that some structures merit re‐interpretation via careful comparison to experimental data. O. Lewinsonet al. (2020) 594: 3799 ‐3814. Credits for the image: Michal Faitelson, Oded Lewinson, Nurit Livnat Levanon. (Source: FEBS Letters)
Source: FEBS Letters - March 23, 2021 Category: Biochemistry Tags: Issue Information Source Type: research

The incredible diversity of structures and functions of ABC transporters
(Source: FEBS Letters)
Source: FEBS Letters - March 23, 2021 Category: Biochemistry Authors: Amro Hamdoun, Ute A. Hellmich, Gergely Szakacs, Karl Kuchler Tags: Editorial Source Type: research