Yuelin Zhang, Jiahui Li, Li Tan, Jun Xue, Yujiang Geno Shi
{"title":"Understanding the role of ten-eleven translocation family proteins in kidney diseases.","authors":"Yuelin Zhang, Jiahui Li, Li Tan, Jun Xue, Yujiang Geno Shi","doi":"10.1042/BST20240291","DOIUrl":"10.1042/BST20240291","url":null,"abstract":"<p><p>Epigenetic mechanisms play a critical role in the pathogenesis of human diseases including kidney disorders. As the erasers of DNA methylation, Ten-eleven translocation (TET) family proteins can oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), thus leading to passive or active DNA demethylation. Similarly, TET family proteins can also catalyze the same reaction on RNA. In addition, TET family proteins can also regulate chromatin structure and gene expression in a catalytic activity-independent manner through recruiting the SIN3A/HDAC co-repressor complex. In 2012, we reported for the first time that the genomic 5-hydroxymethylcytosine level and the mRNA levels of Tet1 and Tet2 were significantly downregulated in murine kidneys upon ischemia and reperfusion injury. Since then, accumulating evidences have eventually established an indispensable role of TET family proteins in not only acute kidney injury but also chronic kidney disease. In this review, we summarize the upstream regulatory mechanisms and the pathophysiological role of TET family proteins in major types of kidney diseases and discuss their potential values in clinical diagnosis and treatment.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2203-2214"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Disruptions to protein kinase A localization in adrenal pathology.","authors":"Mitchell H Omar","doi":"10.1042/BST20240444","DOIUrl":"10.1042/BST20240444","url":null,"abstract":"<p><p>Cell signaling fidelity requires specificity in protein-protein interactions and precise subcellular localization of signaling molecules. In the case of protein phosphorylation, many kinases and phosphatases exhibit promiscuous substrate pairing and therefore require targeting interactions to modify the appropriate substrates and avoid cross-talk among different pathways. In the past 10 years, researchers have discovered and investigated how loss of specific interactions and subcellular targeting for the protein kinase A catalytic subunit (PKAc) lead to cortisol-producing adenomas and the debilitating stress disorder adrenal Cushing's syndrome. This article reviews classical studies regarding PKA localization in glucocorticoid-producing adrenal cells and synthesizes recent evidence of disrupted PKA localization and selective regulatory interactions in adrenal pathology.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2231-2241"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alina Galivondzhyan, Dmitry Sutormin, Vladimir Panteleev, Andrey Kulbachinskiy, Konstantin Severinov
{"title":"The role of prokaryotic argonautes in resistance to type II topoisomerases poison ciprofloxacin.","authors":"Alina Galivondzhyan, Dmitry Sutormin, Vladimir Panteleev, Andrey Kulbachinskiy, Konstantin Severinov","doi":"10.1042/BST20240094","DOIUrl":"10.1042/BST20240094","url":null,"abstract":"<p><p>Argonaute proteins are programmable nucleases found in all domains of life. Eukaryotic argonautes (eAgos) participate in genetic regulation, antiviral response, and transposon silencing during RNA interference. Prokaryotic argonautes (pAgos) are much more diverse than eAgos and have been implicated in defense against invading genetic elements. Recently, it was shown that pAgos protect bacterial cells from a topoisomerase poison ciprofloxacin, raising a possibility that they may play a role in DNA replication and/or repair. Here, we discuss possible models of pAgo-mediated ciprofloxacin resistance. We propose that pAgos could (i) participate in chromosome decatenation as a backup to topoisomerases; (ii) participate in the processing of DNA repair intermediates formed after topoisomerase poisoning, or (iii) induce SOS response that generally affects DNA repair and antibiotic resistance. These hypotheses should guide future investigations of the involvement of pAgos in the emergence of resistance to ciprofloxacin and, possibly, other antibiotics.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2157-2166"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Histone H3 mutations and their impact on genome stability maintenance.","authors":"Lucas D Caeiro, Ramiro E Verdun, Lluis Morey","doi":"10.1042/BST20240177","DOIUrl":"10.1042/BST20240177","url":null,"abstract":"<p><p>Histones are essential for maintaining chromatin structure and function. Histone mutations lead to changes in chromatin compaction, gene expression, and the recruitment of DNA repair proteins to the DNA lesion. These disruptions can impair critical DNA repair pathways, such as homologous recombination and non-homologous end joining, resulting in increased genomic instability, which promotes an environment favorable to tumor development and progression. Understanding these mechanisms underscores the potential of targeting DNA repair pathways in cancers harboring mutated histones, offering novel therapeutic strategies to exploit their inherent genomic instability for better treatment outcomes. Here, we examine how mutations in histone H3 disrupt normal chromatin function and DNA damage repair processes and how these mechanisms can be exploited for therapeutic interventions.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2179-2191"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"How does CHD4 slide nucleosomes?","authors":"Xavier J Reid, Yichen Zhong, Joel P Mackay","doi":"10.1042/BST20230070","DOIUrl":"10.1042/BST20230070","url":null,"abstract":"<p><p>Chromatin remodelling enzymes reposition nucleosomes throughout the genome to regulate the rate of transcription and other processes. These enzymes have been studied intensively since the 1990s, and yet the mechanism by which they operate has only very recently come into focus, following advances in cryoelectron microscopy and single-molecule biophysics. CHD4 is an essential and ubiquitous chromatin remodelling enzyme that until recently has received less attention than remodellers such as Snf2 and CHD1. Here we review what recent work in the field has taught us about how CHD4 reshapes the genome. Cryoelectron microscopy and single-molecule studies demonstrate that CHD4 shares a central remodelling mechanism with most other chromatin remodellers. At the same time, differences between CHD4 and other chromatin remodellers result from the actions of auxiliary domains that regulate remodeller activity by for example: (1) making differential interactions with nucleosomal epitopes such as the acidic patch and the N-terminal tail of histone H4, and (2) inducing the formation of distinct multi-protein remodelling complexes (e.g. NuRD vs ChAHP). Thus, although we have learned much about remodeller activity, there is still clearly much more waiting to be revealed.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1995-2008"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Calcium signaling in mitochondrial intermembrane space.","authors":"Shanikumar Goyani, Shatakshi Shukla, Pooja Jadiya, Dhanendra Tomar","doi":"10.1042/BST20240319","DOIUrl":"10.1042/BST20240319","url":null,"abstract":"<p><p>The mitochondrial intermembrane space (IMS) is a highly protected compartment, second only to the matrix. It is a crucial bridge, coordinating mitochondrial activities with cellular processes such as metabolites, protein, lipid, and ion exchange. This regulation influences signaling pathways for metabolic activities and cellular homeostasis. The IMS harbors various proteins critical for initiating apoptotic cascades and regulating reactive oxygen species production by controlling the respiratory chain. Calcium (Ca2+), a key intracellular secondary messenger, enter the mitochondrial matrix via the IMS, regulating mitochondrial bioenergetics, ATP production, modulating cell death pathways. IMS acts as a regulatory site for Ca2+ entry due to the presence of different Ca2+ sensors such as MICUs, solute carriers (SLCs); ion exchangers (LETM1/SCaMCs); S100A1, mitochondrial glycerol-3-phosphate dehydrogenase, and EFHD1, each with unique Ca2+ binding motifs and spatial localizations. This review primarily emphasizes the role of these IMS-localized Ca2+ sensors concerning their spatial localization, mechanism, and molecular functions. Additionally, we discuss how these sensors contribute to the progression and pathogenesis of various human health conditions and diseases.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2215-2229"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Puck N Norell, Daniele Campisi, Jagan Mohan, Thomas Wollert
{"title":"Biogenesis of omegasomes and autophagosomes in mammalian autophagy.","authors":"Puck N Norell, Daniele Campisi, Jagan Mohan, Thomas Wollert","doi":"10.1042/BST20240015","DOIUrl":"10.1042/BST20240015","url":null,"abstract":"<p><p>Autophagy is a highly conserved catabolic pathway that maintains cellular homeostasis by promoting the degradation of damaged or superfluous cytoplasmic material. A hallmark of autophagy is the generation of membrane cisternae that sequester autophagic cargo. Expansion of these structures allows cargo to be engulfed in a highly selective and exclusive manner. Cytotoxic stress or starvation induces the formation of autophagosomes that sequester bulk cytoplasm instead of selected cargo. This rather nonselective pathway is essential for maintaining vital cellular functions during adverse conditions and is thus a major stress response pathway. Both selective and nonselective autophagy rely on the same molecular machinery. However, due to the different nature of cargo to be sequestered, the involved molecular mechanisms are fundamentally different. Although intense research over the past decades has advanced our understanding of autophagy, fundamental questions remain to be addressed. This review will focus on molecular principles and open questions regarding the formation of omegasomes and phagophores in nonselective mammalian autophagy.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2145-2155"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sneha S Varghese, Alessandro Giovanni Hernandez-De La Peña, Sangeeta Dhawan
{"title":"Safeguarding genomic integrity in beta-cells: implications for beta-cell differentiation, growth, and dysfunction.","authors":"Sneha S Varghese, Alessandro Giovanni Hernandez-De La Peña, Sangeeta Dhawan","doi":"10.1042/BST20231519","DOIUrl":"10.1042/BST20231519","url":null,"abstract":"<p><p>The maintenance of optimal glucose levels in the body requires a healthy reserve of the insulin producing pancreatic beta-cells. Depletion of this reserve due to beta-cell dysfunction and death results in development of diabetes. Recent findings highlight unresolved DNA damage as a key contributor to beta-cell defects in diabetes. Beta-cells face various stressors and metabolic challenges throughout life, rendering them susceptible to DNA breaks. The post-mitotic, long-lived phenotype of mature beta-cells further warrants robust maintenance of genomic integrity. Failure to resolve DNA damage during beta-cell development, therefore, can result in an unhealthy reserve of beta-cells and predispose to diabetes. Yet, the molecular mechanisms safeguarding beta-cell genomic integrity remain poorly understood. Here, we focus on the significance of DNA damage in beta-cell homeostasis and postulate how cellular expansion, epigenetic programming, and metabolic shifts during development may impact beta-cell genomic integrity and health. We discuss recent findings demonstrating a physiological role for DNA breaks in modulating transcriptional control in neurons, which share many developmental programs with beta-cells. Finally, we highlight key gaps in our understanding of beta-cell genomic integrity and discuss emerging areas of interest.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2133-2144"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanisms conferring bacterial cell wall variability and adaptivity.","authors":"Gabriel Torrens, Felipe Cava","doi":"10.1042/BST20230027","DOIUrl":"10.1042/BST20230027","url":null,"abstract":"<p><p>The bacterial cell wall, a sophisticated and dynamic structure predominantly composed of peptidoglycan (PG), plays a pivotal role in bacterial survival and adaptation. Bacteria actively modify their cell walls by editing PG components in response to environmental challenges. Diverse variations in peptide composition, cross-linking patterns, and glycan strand structures empower bacteria to resist antibiotics, evade host immune detection, and adapt to dynamic environments. This review comprehensively summarizes the most common modifications reported to date and their associated adaptive role and further highlights how regulation of PG synthesis and turnover provides resilience to cell lysis.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1981-1993"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Dsc complex and its role in Golgi quality control.","authors":"Yannick Weyer, David Teis","doi":"10.1042/BST20230375","DOIUrl":"10.1042/BST20230375","url":null,"abstract":"<p><p>Membrane proteins play crucial roles in cellular functions. However, processes such as the insertion of membrane proteins into the endoplasmic reticulum (ER), their folding into native structures, the assembly of multi-subunit membrane protein complexes, and their targeting from the ER to specific organelles are prone to errors and have a relatively high failure rate. To prevent the accumulation of defective or orphaned membrane proteins, quality control mechanisms assess folding, quantity, and localization of these proteins. This quality control is vital for preserving organelle integrity and maintaining cellular health. In this mini-review, we will focus on how selective membrane protein quality control at the Golgi apparatus, particularly through the defective for SREBP cleavage (Dsc) ubiquitin ligase complex, detects orphaned proteins and prevents their mis-localization to other organelles.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2023-2034"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}