Biological Chemistry最新文献

The nascent polypeptide-associated complex (NAC) as regulatory hub on ribosomes.

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-04-02 DOI: 10.1515/hsz-2025-0114

Laurenz Rabl, Elke Deuerling

引用次数: 0

Unclogging of the TOM complex under import stress.

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-03-28 DOI: 10.1515/hsz-2025-0110

Joshua Jackson, Thomas Becker

{"title":"Unclogging of the TOM complex under import stress.","authors":"Joshua Jackson, Thomas Becker","doi":"10.1515/hsz-2025-0110","DOIUrl":"https://doi.org/10.1515/hsz-2025-0110","url":null,"abstract":"Mitochondrial functions and biogenesis depend on the import of more than 1,000 proteins which are synthesized as precursor proteins on cytosolic ribosomes. Mitochondrial protein translocases sort the precursor proteins into the mitochondrial sub-compartments: outer and inner membrane, the intermembrane space and the matrix. The translocase of the outer mitochondrial membrane (TOM complex) constitutes the major import site for most of these precursor proteins. Defective protein translocases, premature folding of the precursor, or depletion of the membrane potential can cause clogging of the TOM channel by a precursor protein. This clogging impairs further protein import and leads to accumulation of precursor proteins in the cell that perturbates protein homeostasis, leading to proteotoxic stress in the cell. Therefore, unclogging of the translocon is critical for maintaining mitochondrial and cellular function. Ubiquitylation and AAA-ATPases play a central role in the extraction of the precursor proteins to deliver them to the proteasome for degradation. Here we summarize our understanding of the molecular mechanisms that remove such translocation-stalled precursor proteins from the translocation channel to regenerate the TOM complex for protein import.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GPI-anchored serine proteases: essential roles in development, homeostasis, and disease.

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-03-17 DOI: 10.1515/hsz-2024-0135

Joseph G Lundgren, Michael G Flynn, Karin List

引用次数: 0

Unfolded protein responses in Chlamydomonas reinhardtii.

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-03-13 DOI: 10.1515/hsz-2025-0101

Sarah Gabelmann, Michael Schroda

{"title":"Unfolded protein responses in Chlamydomonas reinhardtii.","authors":"Sarah Gabelmann, Michael Schroda","doi":"10.1515/hsz-2025-0101","DOIUrl":"https://doi.org/10.1515/hsz-2025-0101","url":null,"abstract":"The disruption of protein homeostasis leads to the increased un- and misfolding of proteins and the formation of toxic protein aggregates. Their accumulation triggers an unfolded protein response that is characterized by the transcriptional upregulation of molecular chaperones and proteases, and aims to restore proteome integrity, maintain cellular function, suppress the cause of perturbation, and prevent disease and death. In the green microalga Chlamydomonas reinhardtii, the study of this response to proteotoxic stress has provided insights into the function of chaperone and protease systems, which are, though simpler, closely related to those found in land plants. In addition, there has been considerable progress in understanding the triggers and regulation of compartment-specific unfolded protein responses. This review provides an overview on how the dysfunction of protein homeostasis is sensed in the different compartments of Chlamydomonas, and summarizes the current knowledge on the pathways that are triggered to restore equilibrium in the cell, while also highlighting similarities and differences to the unfolded protein responses of other model organisms.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How neurons cope with oxidative stress.

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-02-25 DOI: 10.1515/hsz-2024-0146

Johannes Ebding, Fiorella Mazzone, Stefan Kins, Jan Pielage, Tanja Maritzen

{"title":"How neurons cope with oxidative stress.","authors":"Johannes Ebding, Fiorella Mazzone, Stefan Kins, Jan Pielage, Tanja Maritzen","doi":"10.1515/hsz-2024-0146","DOIUrl":"10.1515/hsz-2024-0146","url":null,"abstract":"Neurons are highly dependent on mitochondrial respiration for energy, rendering them vulnerable to oxidative stress. Reactive oxygen species (ROS), by-products of oxidative phosphorylation, can damage lipids, proteins, and DNA, potentially triggering cell death pathways. This review explores the neuronal vulnerability to ROS, highlighting metabolic adaptations and antioxidant systems that mitigate oxidative damage. Balancing metabolic needs and oxidative stress defenses is critical for neurons, as disruptions are implicated in neurodegenerative diseases. Neurons uniquely modulate metabolic pathways, favoring glycolysis over oxidative phosphorylation in cell bodies, to minimize harmful ROS production. Key antioxidants, including superoxide dismutases and glutathione peroxidases, play crucial roles in neuronal protection, as evident from genetic studies linking deficiencies to neurodegeneration. Notably, neurons have the ability to adapt to oxidative conditions in compartment-specific manners and also utilize ROS as a signaling molecule to promote adaptive synaptic plasticity. Future research should aim to elucidate differential ROS signaling and antioxidant responses across neuronal compartments for improved therapeutic strategies.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Broadened substrate specificity of bacterial dipeptidyl-peptidase 7 enables release of half of all dipeptide combinations from peptide N-termini.

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-02-10 DOI: 10.1515/hsz-2024-0156

Kana Shirakura, Takayuki K Nemoto, Yuko Ohara Nemoto, Haruka Nishimata, Momo Sawase, Yu Shimoyama, Manami Nakasato-Suzuki, Kiyoshi Ito, Naomi Tanoue

{"title":"Broadened substrate specificity of bacterial dipeptidyl-peptidase 7 enables release of half of all dipeptide combinations from peptide N-termini.","authors":"Kana Shirakura, Takayuki K Nemoto, Yuko Ohara Nemoto, Haruka Nishimata, Momo Sawase, Yu Shimoyama, Manami Nakasato-Suzuki, Kiyoshi Ito, Naomi Tanoue","doi":"10.1515/hsz-2024-0156","DOIUrl":"10.1515/hsz-2024-0156","url":null,"abstract":"Dipeptide production mediated by dipeptidyl-peptidase (DPP)4, DPP5, DPP7, and DPP11 plays a crucial role in growth of Porphyromonas gingivalis, a periodontopathic asaccharolytic bacterium. Given the particular P1-position specificity of DPPs, it has been speculated that DPP5 or DPP7 might be responsible for degrading refractory P1 amino acids, i.e., neutral (Thr, His, Gly, Ser, Gln) and hydrophilic (Asn) residues. The present results identified DPP7 as an entity that processes these residues, thus ensuring complete production of nutritional dipeptides in the bacterium. Activity enhancement by the P1' residue was observed in DPP7, as well as DPP4 and DPP5. Toward the refractory P1 residues, DPP7 uniquely hydrolyzed HX|LD-MCA (X = His, Gln, or Asn) and their hydrolysis was most significantly suppressed in dpp7 gene-disrupted cells. Additionally, hydrophobic P2 residue significantly enhanced DPP7 activity toward these substrates. The findings propose a comprehensive 20 P1 × 20 P2 amino acid matrix showing the coordination of four DPPs to achieve complete dipeptide production along with subsidiary peptidases. The present finding of a broad substrate specificity that DPP7 accounts for releasing 48 % (192/400) of N-terminal dipeptides could implicate its potential role in linking periodontopathic disease to related systemic disorders.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protein kinase CK2 contributes to glucose homeostasis.

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-02-07 DOI: 10.1515/hsz-2024-0158

Claudia Götz, Mathias Montenarh

{"title":"Protein kinase CK2 contributes to glucose homeostasis.","authors":"Claudia Götz, Mathias Montenarh","doi":"10.1515/hsz-2024-0158","DOIUrl":"10.1515/hsz-2024-0158","url":null,"abstract":"In the early days of CK2 research, it was already published that the affinity of CK2 for its substrate casein was affected by insulin. Subsequent to the discovery of inhibitors of CK2 kinase activity, it was shown that CK2 has an influence on hormones that regulate glucose homeostasis and on enzymes that influence glucose metabolism in pancreatic islet cells as well as in hormone-sensitive target cells. This regulation includes the influence on transcription factors and thereby, gene expression, as well as direct modulation of the catalytic activity. The used CK2 inhibitors, especially the older ones, show a broad range of specificity, selectivity and off-target effects. Recently applied methods to down-regulate the expression of individual CK2 subunits using siRNA or CRISPR/Cas9 technology have contributed to the improvement of specificity. It was shown that inhibition of CK2 kinase activity or knock-down or knock-out of CK2α leads to an elevated synthesis and secretion of insulin in pancreatic β-cells and a down-regulation of the synthesis and secretion of glucagon from pancreatic α-cells. In the present review CK2-dependent molecular mechanisms will be addressed which contribute to the maintenance of glucose homeostasis.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MitoStores: stress-induced aggregation of mitochondrial proteins. 线粒体：应激诱导的线粒体蛋白聚集。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-01-21 DOI: 10.1515/hsz-2024-0148

Pragya Kaushik, Johannes M Herrmann, Katja G Hansen

{"title":"MitoStores: stress-induced aggregation of mitochondrial proteins.","authors":"Pragya Kaushik, Johannes M Herrmann, Katja G Hansen","doi":"10.1515/hsz-2024-0148","DOIUrl":"10.1515/hsz-2024-0148","url":null,"abstract":"Most mitochondrial proteins are synthesized in the cytosol and post-translationally imported into mitochondria. If the rate of protein synthesis exceeds the capacity of the mitochondrial import machinery, precursor proteins can transiently accumulate in the cytosol. The cytosolic accumulation of mitochondrial precursors jeopardizes cellular protein homeostasis (proteostasis) and can be the cause of diseases. In order to prevent these toxic effects, most non-imported precursors are rapidly degraded by the ubiquitin-proteasome system. However, cells employ a second layer of defense which is the facilitated sequestration of mitochondrial precursor proteins in transient protein aggregates. The formation of such structures is triggered by nucleation factors such as small heat shock proteins. Disaggregases and chaperones can liberate precursors from cytosolic aggregates to pass them on to the mitochondrial import machinery or, under persistent stress conditions, to the proteasome for degradation. Owing to their role as transient buffering systems, these aggregates were referred to as MitoStores. This review articles provides a general overview about the MitoStore concept and the early stages in mitochondrial protein biogenesis in yeast and, in cases where aspects differ, in mammalian cells.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Revival of the Escherichia coli heat shock response after two decades with a small Hsp in a critical but distinct act. 大肠杆菌热休克反应在小热休克二十年后的复苏是一个关键但独特的行为。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-01-07 DOI: 10.1515/hsz-2024-0140

Tsukumi Miwa, Hideki Taguchi

引用次数: 0

Bioprospecting hydroxylated chalcones in in vitro model of ischemia-reoxygenation and probing NOX4 interactions via molecular docking. 羟基查尔酮在体外缺血-再氧化模型中的生物探测及NOX4分子对接的相互作用。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-12-23 Print Date: 2024-12-17 DOI: 10.1515/hsz-2024-0068

Arif Ali, Igor Moreira de Almeida, Emanuel Paula Magalhães, Jesyka Macedo Guedes, Francisco Ferdinando Mesquita Cajazeiras, Marcia Machado Marinho, Emmanuel Silva Marinho, Ramon Róseo Paula Pessoa Bezerra de Menezes, Tiago Lima Sampaio, Hélcio Silva Dos Santos, Geraldo Bezerra da Silva Júnior, Alice Maria Costa Martins

{"title":"Bioprospecting hydroxylated chalcones in in vitro model of ischemia-reoxygenation and probing NOX4 interactions via molecular docking.","authors":"Arif Ali, Igor Moreira de Almeida, Emanuel Paula Magalhães, Jesyka Macedo Guedes, Francisco Ferdinando Mesquita Cajazeiras, Marcia Machado Marinho, Emmanuel Silva Marinho, Ramon Róseo Paula Pessoa Bezerra de Menezes, Tiago Lima Sampaio, Hélcio Silva Dos Santos, Geraldo Bezerra da Silva Júnior, Alice Maria Costa Martins","doi":"10.1515/hsz-2024-0068","DOIUrl":"10.1515/hsz-2024-0068","url":null,"abstract":"Ischemia/reperfusion injury (I/R) is a leading cause of acute kidney injury (AKI) in conditions like kidney transplants, cardiac surgeries, and nephrectomy, contributing to high global mortality and morbidity. This study aimed to analyze the protective effects of 2'-hydroxychalcones in treating I/R-induced AKI by targeting key pathological pathways. Considering strong antioxidant action along with other pharmacological roles of chalcone derivatives, six 2'-hydroxychalcones were synthesized via Claisen-Schmidt condensation and analyzed for their protective effects in an I/R induced AKI model using HK-2 cells. Among six 2'-hydroxychalcones, chalcone A4 significantly increased the HK-2 cells viability compared to I/R group. Chalcone A4 reduced the cell death events by reducing generation of cytoplasmic ROS and mitochondrial transmembrane potential. It also increased GSH and SOD activity while reducing TBARS levels, indicating strong antioxidant action. Scanning electron microscope images showed that chalcone A4 reversed I/R-induced morphological changes in HK-2 cells, including apoptotic blebbing and cytoplasmic fragmentation. Furthermore, in silico studies revealed interactions with NADPH oxidase 4, further supporting its protective role in I/R-induced AKI. These results showed that chalcone A4 possess potential protective action against I/R induced cellular damage possibly due to its strong antioxidant action and potential interaction with NOX4 subunit of NADPH oxidase.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"727-743"},"PeriodicalIF":2.9,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0