{"title":"Correction to: Innate immune signals triggered on organelle membranes.","authors":"","doi":"10.1093/jb/mvaf035","DOIUrl":"https://doi.org/10.1093/jb/mvaf035","url":null,"abstract":"","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484533","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}
{"title":"Transcriptional control of brown adipocyte differentiation and function by NFIA: recent perspectives on deciphering metabolic diseases.","authors":"Yuta Hiraike","doi":"10.1093/jb/mvaf038","DOIUrl":"https://doi.org/10.1093/jb/mvaf038","url":null,"abstract":"<p><p>Brown adipocytes dissipate chemical energy as heat and confer protection against type 2 diabetes and obesity. Nuclear factor I-A (NFIA) is a transcription factor that orchestrates the brown fat gene program by activating cell-type-specific enhancers and facilitating the genomic binding of PPARγ, the master regulator of adipogenesis, to these enhancers. NFIA promotes mitochondrial oxidative phosphorylation and thermogenesis, while reciprocally suppressing adipose tissue inflammation, thereby contributing to the maintenance of glucose and body weight homeostasis in mice. Here the author provides an overview of the identification of NFIA as a pivotal regulator of brown adipocyte biology, elucidates its underlying mechanisms of action, examines its implications for systemic metabolism, and outlines future perspectives for research in this field.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528141","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}
{"title":"Mitochondrial DNA: leakage, recognition, and associated human diseases.","authors":"Hyota Takamatsu","doi":"10.1093/jb/mvaf037","DOIUrl":"https://doi.org/10.1093/jb/mvaf037","url":null,"abstract":"<p><p>Mitochondria are intracellular organelles originating from intracellular symbiotic bacteria that play essential roles in life activities such as energy production, metabolism, Ca2+ storage, signal transduction, and cell death. Mitochondria also function as hubs for host defense against harmful stimuli such as infection and inflammation control. However, when cells are exposed to stress, mitochondrial homeostasis is disrupted, and mitochondrial DNA (mtDNA) can leak into the cytoplasm or extracellular space. Leaked mtDNA activates innate immune sensors, causing severe inflammation and contributing to the pathogenesis of human diseases. In this review, we summarize the mechanisms by which mtDNA leaks from the mitochondria and subsequently induces inflammation. We also review the relationship between mtDNA leakage and human diseases.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512024","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}
{"title":"Crystal structure of Klebsiella pneumoniae maltohexaose-producing α-amylase.","authors":"Zui Fujimoto, Naomi Kishine, Mitsuru Momma","doi":"10.1093/jb/mvaf034","DOIUrl":"https://doi.org/10.1093/jb/mvaf034","url":null,"abstract":"<p><p>The α-amylase from Klebsiella pneumoniae (KpAmy13), which belongs to glycoside hydrolase family 13 subfamily 19, produces maltohexaose as an initial product when acting on starch and has been characterized as a maltohexaose-producing α-amylase. The crystal structure of KpAmy13 was determined at a resolution of 1.9 Å, revealing the structures of all its domains: N, A, B, and C. Domain N resembles the starch-binding domain known as carbohydrate-binding module family 69, found in α-glucan-related proteins. Although domain N does not conserve the starch-binding residues observed in other proteins, it has several hydrophobic residues on its surface, which might be involved in promoting catalysis. The catalytic cleft is located at the bottom of a circular depression. The domain N-truncated mutant of KpAmy13 in complex with maltohexaose showed that its non-reducing end glucose docks at subsite -6. The long and complex structure of domain B contributes to forming a cleft of the right size for six glucose moieties, demonstrating the exo-acting mechanism.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505775","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}
{"title":"Maintaining a neutral range disperses myosin molecules under salt-free conditions.","authors":"Toru Hayakawa, Yu Shishido, Yuki Ikeuchi, Jun-Ichi Wakamatsu, Haruto Kumura","doi":"10.1093/jb/mvaf036","DOIUrl":"https://doi.org/10.1093/jb/mvaf036","url":null,"abstract":"<p><p>Skeletal muscle myosin is generally considered insoluble under physiological, low ionic strength, or salt-free conditions due to its tendency to self-assemble into filamentous polymers in vitro. Our previous study showed that myosin can be solubilized in low ionic strength solutions containing l-histidine. However, another report suggested that 1-methylhistidine could not solubilize myosin, and the factors essential for myosin solubilization remain unclear. To elucidate the role of l-histidine in the water solubilization of myosin, we examined myosin solubility and the molecular properties of its rod domain, l-meromyosin, using structurally related buffer compounds. Under salt-free conditions, solubility depended heavily on the acid dissociation constant of buffer, indicating that maintaining a neutral pH is critical. The rod domain showed molecular elongation regardless of the buffer type, yet surface charge and hydrophobicity remained comparable to conditions with high ionic strength. These results suggest that myosin is inherently soluble and maintains its structural integrity under neutral, salt-free conditions. The apparent insolubility under such conditions is likely to result from hydrochloric acid used for pH adjustment. Since l-histidine and imidazole achieve neutrality without acid addition, they are ideal buffers for myosin solubilization.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505776","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}
{"title":"Transcription and translation efficiency is reduced in cholesterol-containing liposomes.","authors":"Shota Fukuoka, Ayu Shimomura, Yuya Katsumura, Masaya Oki, Gakushi Tsuji","doi":"10.1093/jb/mvaf032","DOIUrl":"https://doi.org/10.1093/jb/mvaf032","url":null,"abstract":"<p><p>Cholesterol is a crucial lipid that lowers the phase transition temperature of phospholipid membranes and enhances their stability. Artificial cells with diverse functionalities have been developed by encapsulating transcription-translation reactions within liposomes, with the expectation that cholesterol would similarly contribute to the stabilization of membrane compartments in these artificial cells. In this study, we examined whether cholesterol influences the efficiency of reactions within liposomes. Our results demonstrated that the efficiency of transcription-translation reactions decreases in liposomes containing 40 mol% cholesterol, a level comparable to that of the outer leaflet of the human cell membrane. Furthermore, this decrease in reaction efficiency was found to be independent of liposome size or the efficiency of molecule encapsulation. This study highlights the critical role of cholesterol content in the design of artificial cells and drug delivery systems via liposome fusion, emphasizing the need for careful optimization.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284439","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}
{"title":"Bisecting GlcNAc modification of angiotensin-related glycoproteins in mouse kidney.","authors":"Haruka Kawade, Wanxue Bao, Yuko Tokoro, Yoshimasa Ito, Yudai Tsuji, Kazuo Takahashi, Kazuki Nakajima, Miyako Nakano, Yasuhiko Kizuka","doi":"10.1093/jb/mvaf033","DOIUrl":"https://doi.org/10.1093/jb/mvaf033","url":null,"abstract":"<p><p>Structural variations of N-glycans critically regulate glycoprotein functions and are involved in various human diseases. N-Acetylglucosaminyltransferase-III (GnT-III or MGAT3) is highly expressed in the brain and kidney and is an N-glycan branching enzyme that biosynthesizes the unique N-glycan branch designated as bisecting GlcNAc. Its roles in Alzheimer's disease and cancer have been revealed, but the functions of bisecting GlcNAc in the kidney are poorly understood. Here, we show that kidneys in the GnT-III-knockout (KO) mouse exhibit impaired body fluid balance and present interstitial edema. To understand the molecular mechanisms further, we biochemically purified the glycoproteins modified by GnT-III in the mouse kidney and identified these proteins using proteomics. We found that the proteins involved in the pathway for angiotensin II (Ang II) metabolism are modified by GnT-III, and that the subcellular localization of angiotensin converting enzyme was altered in GnT-III-KO cells. Furthermore, the pathology in models of Ang II-related disease was slightly more severe in GnT-III-KO than in wild-type mice. Our data indicate a protective role for bisecting GlcNAc in the mouse kidney, highlighting a newly described link between specific N-glycan structures and renal functions.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284438","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}
{"title":"Differential regulation between photosynthetic type and non-photosynthetic type Fd:FNRs in the negative cooperativity and pH dependency of the electron transfer activity.","authors":"Yoko Kimata-Ariga, Shunsuke Miyake, Takato Murakami, Shunsuke Kuwano","doi":"10.1093/jb/mvaf031","DOIUrl":"https://doi.org/10.1093/jb/mvaf031","url":null,"abstract":"<p><p>In higher plants, ferredoxin (Fd) and Fd-NADP+ reductase (FNR) are each present as distinct isoproteins of photosynthetic type and non-photosynthetic type, which exhibit differential function despite their similarity in the 3D structures. In this study, we addressed differential regulation of Fd/FNR reaction between the two types from two perspectives and investigated the amino acid residues of Fd responsible for the differences. Firstly, pH-dependent profile of Fd/FNR electron transfer activity varied among the combinations of the two types of Fd and FNR; non-photosynthetic type FNR showed similar pattern for the two types of Fds while photosynthetic type FNR was previously shown to exhibit opposite pattern which was explained by the different pH-dependent profile of Km for the two Fds. Secondly, the extent of the suppression of the affinity (in terms of Km value) between Fd and FNR by NADPH significantly varied among the combinations of the two types of Fd:FNR. The difference was shown to be mainly due to the different property of Fd between the two types. Kinetic analyses using site-directed mutants of Fd showed the contribution of C-terminal residues, together with that of 78th residue of Fd, on the differential profile of Fd/FNR reaction by pH and NADPH.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258162","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}
{"title":"Three glutamic acid residues in the cytoplasmic N-terminal tail of long-form GlcAT-P define Golgi-to-ER trafficking.","authors":"Ayaka Okada, Risa Harui, Tomonari Ishida, Katsuaki Higashi, Motohiro Nonaka, Shogo Oka, Jyoji Morise","doi":"10.1093/jb/mvaf030","DOIUrl":"https://doi.org/10.1093/jb/mvaf030","url":null,"abstract":"<p><p>Glucuronyltransferase GlcAT-P is a rate-limiting enzyme involved in the biosynthesis of the Human Natural Killer-1 carbohydrate and is essential for acquiring higher brain functions. Alternative splicing produces two isoforms, short-form GlcAT-P (sGlcAT-P) and long-form GlcAT-P (lGlcAT-P), which share identical peptide sequences except for an additional 13 amino acids (AA) in the cytoplasmic N-terminal tail of lGlcAT-P. Although sGlcAT-P localizes to the Golgi apparatus (GA), where many glycosyltransferases reside, lGlcAT-P is distributed in both the GA and endoplasmic reticulum (ER). However, the mechanisms responsible for this distinct intracellular distribution remain poorly understood. In this study, we explored the role of the 13 AA in the cytoplasmic N-tail of lGlcAT-P in trafficking between the GA and the ER using the Retention Using Selective Hooks system. Our findings revealed that lGlcAT-P undergoes enhanced retrograde trafficking from the GA to the ER, whereas its anterograde trafficking from the ER to the GA remains largely unaffected. In addition, three glutamic acid residues within the 13 AA of lGlcAT-P were identified as crucial for promoting retrograde trafficking. These results suggest that the ER distribution of lGlcAT-P is primarily governed by Golgi-to-ER trafficking regulated by specific sequences in its cytoplasmic N-tail.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248033","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}
{"title":"Suicide substrate reaction-like modification of mouse serine racemase with L-serine.","authors":"Akari Hata, Tomokazu Ito, Hitoshi Mori, Takuya Ogawa, Tatsuo Kurihara, Hisashi Hemmi, Tohru Yoshimura","doi":"10.1093/jb/mvaf019","DOIUrl":"10.1093/jb/mvaf019","url":null,"abstract":"<p><p>A pyridoxal 5'-phosphate-dependent fold-type II serine racemase (SR) is responsible for the synthesis of D-Ser, which serves as a co-agonist of N-methyl-D-aspartate glutamate receptor. In addition to racemization, SR catalyzes the dehydration of D- and L-Ser. SR is suggested to be involved in the D-Ser degradation in vivo, but this has not been confirmed. In this study, we found that mouse SR (mSR) underwent a suicide substrate reaction-like modification with its substrate, resulting in a remarkable change in its reaction specificity. mSR gradually lost its activity by the incubation with L- and D-Ser, but not completely. mSR was labelled with [14C]-L-Ser. ESI-MS analysis revealed that the molecular mass of SR increased by 84 Da by the incubation with L-Ser. Taken together with the results of previous crystallographic studies of fission yeast SR, we concluded that the active site lysine residue of mSR was modified with an α-aminoacrylate intermediate generated from L-Ser and converted to a lysinoalanine residue. The modification significantly decreased the racemization and L-Ser dehydration activities, while dramatically increased the D-Ser dehydration activity by the ~100 times reduction of the Km value. This is probably advantageous for the D-Ser degradation by mSR under physiological conditions.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"437-445"},"PeriodicalIF":2.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998817","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}