Review
Cell Biology
Ryan J. J. Mailloux, Cathryn Grayson, Olivia Koufos
Summary: Protein S-glutathionylation has been proposed as a regulator of cell metabolism for four decades. This redox-sensitive covalent modification serves as a cell-wide signaling platform and plays a key role in embryonic development and regulation of physiological functions. It functions as a feedback loop for inhibiting mitochondrial hydrogen peroxide (H2O2) production and desensitizing mitochondrial redox signals.
Article
Biochemistry & Molecular Biology
Syed Husain Mustafa Rizvi, Di Shao, Yuko Tsukahara, David Richard Pimentel, Robert M. Weisbrod, Naomi M. Hamburg, Mark E. McComb, Reiko Matsui, Markus Michael Bachschmid
Summary: The study showed that exposure to hydrogen peroxide induced S-glutathionylation and nuclear translocation of GAPDH in HEK 293T cells. Overexpression of Glrx or a redox dead mutant GAPDH inhibited S-glutathionylation and nuclear translocation. Nuclear GAPDH formed a complex with SirT1, transferring S-glutathionylation to SirT1 and inhibiting its deacetylase activity to initiate apoptotic signaling.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Huimin Zhu, Changyang Yan, Peng Yao, Ping Li, Yi Li, Hua Yang
Summary: Rg1 protects against septic cardiac injury by maintaining OPA1 stability and preserving mitochondrial cristae structure. It inhibits S-glutathionylation of OPA1 by interacting with GSTP1, thereby promoting OPA1-Mitofilin interaction and protecting mitochondrial structure.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Chemistry, Analytical
Minggang Tian, Baoli Dong, Zheming Zhang, Junling Yin, Weiying Lin
Summary: A new fluorescent probe mPTP-F has been successfully designed to monitor the opening of mPTP in cellular native status. This probe can serve as an important tool for studying areas such as ischemia-reperfusion injury and cell apoptosis.
ANALYTICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Dong-Oh Moon
Summary: This review provides a comprehensive analysis of the multifaceted role of calcium in apoptosis regulation, focusing on its associated signaling pathways and molecular mechanisms. It explores the impact of calcium on apoptosis through its effects on various cellular compartments and highlights its connection to ER stress. Additionally, it discusses the interplay between calcium and proteins such as calpains, calmodulin, and Bcl-2 family members, and its role in regulating caspase activation and pro-apoptotic factor release. Understanding the complex relationship between calcium and apoptosis is crucial for identifying potential treatment options for diseases associated with imbalanced cell death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Environmental Sciences
Lin Che, Chuan-Li Yang, Yu Chen, Zi-Li Wu, Ze-Bang Du, Jia-Shen Wu, Cong-Ling Gan, Si-Ping Yan, Jing Huang, Ni-Jun Guo, Yu-Chun Lin, Zhong-Ning Lin
Summary: Cadmium exposure disrupts mitochondrial redox balance, leading to increased mitoROS levels and enhanced S-glutathionylation of Mfn2, ultimately inducing neuronal necroptosis. Antioxidant intervention can reduce S-glutathionylation of Mfn2 and antagonize Cd-induced necroptosis and neurotoxicity.
Review
Pharmacology & Pharmacy
Xia Li, Yan Ma, Junzhou Wu, Maowei Ni, Aiping Chen, Yun Zhou, Wumin Dai, Zhongjian Chen, Ruibin Jiang, Yutian Ling, Qinghua Yao, Wei Chen
Summary: 5-Fluorouracil (5-Fu) is a first-line drug for colorectal cancer (CRC) therapy. However, the development of 5-Fu resistance limits its effectiveness and leads to poor prognosis. Transglutaminase 2 (TGM2) is associated with chemoresistance in CRC and is regulated by thiol oxidative stress. Upregulation of thiol oxidative stress reverses 5-Fu resistance through downregulation of TGM2 and enhances apoptosis. TGM2 may serve as a potential therapeutic target for treating 5-Fu-resistant CRC.
DRUG RESISTANCE UPDATES
(2023)
Article
Neurosciences
Jiahe Wang, Siyuan Yang, Haiying Li, Haitao Shen, Xiaocheng Lu, Xiang Li, Gang Chen
Summary: This study found that mitochondrial calcium uptake family 3 (MICU3) plays an important role in intracerebral hemorrhage (ICH). Through in vivo and in vitro models, it was observed that MICU3 expression increased in ICH. Knockdown of MICU3 significantly reduced mitochondrial calcium uptake, attenuated cell apoptosis, and decreased reactive oxygen species accumulation. The downregulation of MICU3 also promoted recovery of neurobehavioral and cognitive function. These findings highlight the significance of MICU3 in cell apoptosis, oxidative stress, and maintenance of mitochondrial structure and function, making it a potential molecular marker and therapeutic target for ICH.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Christian Sirko, Matthew J. Novello, Peter B. Stathopulos
Summary: Stromal interaction molecule 1 (STIM1) is a calcium sensing protein that regulates store-operated calcium entry. S-Glutathionylation of STIM1 at Cys49 or Cys56 induces conformational changes and thermodynamic destabilization. This modification or mutation of Cys56 reduces the binding affinity to calcium ions.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Alex G. Gauthier, Mosi Lin, Sidorela Zefi, Abhijit Kulkarni, Ganesh A. Thakur, Charles R. Ashby Jr, Lin L. Mantell
Summary: Supraphysiological concentrations of oxygen (hyperoxia) can compromise host defense and increase susceptibility to bacterial and viral infections, causing ventilator-associated pneumonia (VAP). GAT107, a novel alpha 7nAChR agonistic positive allosteric modulator, significantly decreased animal mortality and markers of inflammatory injury in mice exposed to hyperoxia and subsequently infected with Pseudomonas aeruginosa. GAT107 restored hyperoxia-compromised phagocytic functions by decreasing HMGB1 release, most likely via a mitochondrial-directed pathway, suggesting it as a potential treatment for acute inflammatory lung injury.
Article
Multidisciplinary Sciences
Emmanouil Zacharioudakis, Bogos Agianian, Vasantha Kumar Mv, Nikolaos Biris, Thomas P. Garner, Inna Rabinovich-Nikitin, Amanda T. Ouchida, Victoria Margulets, Lars Ulrik Nordstrom, Joel S. Riley, Igor Dolgalev, Yun Chen, Andre J. H. Wittig, Ryan Pekson, Chris Mathew, Peter Wei, Aristotelis Tsirigos, Stephen W. G. Tait, Lorrie A. Kirshenbaum, Richard N. Kitsis, Evripidis Gavathiotis
Summary: Mitofusins are proteins that regulate mitochondrial fusion, a process with significant impact on cellular processes. This study identifies small molecules that can activate or inhibit Mitofusins' activity, thereby modulating mitochondrial fusion and functionality. Inhibition of mitochondrial fusion leads to certain physiological changes such as caspase-3/7 activation and DNA damage. The findings highlight the importance of Mitofusins' conformational changes and oligomerization in enabling mitochondrial fusion. The study provides insights into the function and regulation of Mitofusins and offers potential small molecules for pharmacological targeting.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Elena Kalinina, Maria Novichkova
Summary: S-glutathionylation and S-nitrosylation are reversible post-translational modifications on the cysteine thiol groups of proteins, important for regulating protein functional activity and cellular processes. The connection and switch functions between these modifications are performed by GSNO, dependent on factors like GSH content, GSH/GSSG ratio, and cellular redox state. Trx family enzymes play a crucial role in regulating these processes, with their activity determined by cellular redox status and GSH/GSSG ratio.
Review
Biochemistry & Molecular Biology
Rahul Raj Singh, Katie M. Reindl
Summary: The GST protein family in humans plays a crucial role in antioxidant defense, with overactive GST proteins commonly observed in many human cancers, contributing to tumorigenesis through various processes. Structural and pharmacological studies have identified GST inhibitors that are currently in clinical trials for cancer treatment and other diseases.
Article
Cardiac & Cardiovascular Systems
Peiran Zhang, Xianchun Yan, Xiaoyan Zhang, Yuan Liu, Xingxing Feng, Ziyan Yang, Jiayulin Zhang, Xinyuan Xu, Qijun Zheng, Liang Liang, Hua Han
Summary: TMEM215 is induced by blood flow-derived shear stress through downregulating EZH2. TMEM215 protects endothelial cells (ECs) from BIK-triggered mitochondrial apoptosis mediated by calcium influx through mitochondria-associated ER membranes during vessel pruning. Loss of Tmem215 in ECs promotes vascular regression and inhibits tumor growth, but attenuates lung metastasis.
CIRCULATION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Na Li, JuYuan Wang, XiaoLing Zang, ZhaoYang Wang, Tao Zhang, BaoXiang Zhao, JunYing Miao, ZhaoMin Lin
Summary: This study revealed that CPC inhibits autophagy and promotes apoptosis by inhibiting Nrf2 activation, dependent on endogenous H2S. Furthermore, CPC inhibits Nrf2 nucleus translocation by inhibiting glutathionylation of Keap1, leading to suppression of cancer cell growth.
Article
Biochemistry & Molecular Biology
G. F. Senguel, R. Mishra, E. Candiello, P. Schu
Summary: AP2 forms AP2 CCV with clathrin and other coat proteins, and synapses contain different types of CCV. The stability and composition of CCV are regulated by various factors, including Hsc70 and phosphorylation patterns. The knockout of the AP1/O1B complex disrupts synaptic vesicle recycling and endosomal protein sorting, leading to upregulation of endocytosis. Stable CCV, termed stCCV, have distinct characteristics and specialized functions in synaptic plasticity. The phosphorylation of Hsc70 and the levels of kinases play a crucial role in regulating the stability and disassembly of clathrin in CCV.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Martin Fluck, Colline Sanchez, Vincent Jacquemond, Christine Berthier, Marie-Noelle Giraud, Daniel Jacko, Kathe Bersiner, Sebastian Gehlert, Guus Baan, Richard T. Jaspers
Summary: Enhancing CaMKII signaling improves fatigue resistance and contractile characteristics of skeletal muscle by enhancing calcium release.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Letter
Biochemistry & Molecular Biology
Federica Coppola, Sara Monaci, Alessandro Falsini, Carlo Aldinucci, Irene Filippi, Daniela Rossi, Fabio Carraro, Antonella Naldini
Summary: The adaptor protein p62 plays a crucial role in maintaining the survival of dendritic cells (DCs) under hypoxic conditions by preserving Erk1/2 phosphorylation and reducing AMPK activation, thus extending their lifespan to ensure their functions in hypoxic microenvironments.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Jenifer Pendiuk Goncalves, Jorvani Cruz Villarreal, Sierra A. Walker, Xuan Ning Sharon Tan, Chad Borges, Joy Wolfram
Summary: This study used a mass spectrometry-based approach to assess the differences in glycan features between extracellular vesicles (EVs) and originating cells. The results showed that EVs selectively enriched specific glycan features, particularly those associated with binding to the extracellular matrix. The study also found differences in EV glycan sorting between different metastatic cell lines and mouse models, indicating a potential role of glycan diversity in the metastatic process.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
De-ao Gong, Peng Zhou, Wen-yi Chang, Jia-yao Yang, Yan-lai Zhang, Ai-long Huang, Ni Tang, Kai Wang
Summary: Liver cancer, ranked sixth globally, is a major contributor to cancer-related mortality. Metastasis is the main cause of treatment failure and deaths in liver cancer. The SPOP-CREB5-MET axis plays a significant role in liver cancer metastasis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Ning Huang, Jun Tang, Xiaoyao Yi, Maoxin Zhang, Bin Li, Yuan Cheng, Jin Chen
Summary: This study reveals that glioma-derived S100A9 can induce microglial M2 polarization, inhibit CD8+ T lymphocytes, and promote immunosuppression. The mechanism is related to the interaction with alpha v133 integrin and subsequent activation of AKT1 in microglia. The expression of S100A9 is positively associated with CD206 expression and negatively correlated with CD8+ T lymphocyte accumulation in the TME, suggesting a potential role of S100A9 in regulating the tumor microenvironment and immune evasion in glioma.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Yomna S. Abd El-Aziz, Matthew J. McKay, Mark P. Molloy, Betty McDowell, Elizabeth Moon, Loretta Sioson, Amy Sheen, Angela Chou, Anthony J. Gill, Patric J. Jansson, Sumit Sahni
Summary: This study identified a novel combination of autophagy inhibitors that can effectively inhibit the proliferation of oral squamous cell carcinoma (OSCC) cells, including both chemosensitive and chemoresistant cells. This research is important for the development of new therapies for advanced OSCC tumors.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Luojia Liu, Xiaoqiang Liu, Ying Chen, Meng Kong, Jinghong Zhang, Min Jiang, Hongling Zhou, Jinrui Yang, Xu Chen, Ze Zhang, Chao Wu, Xupin Jiang, Jiaping Zhang
Summary: Our study revealed that the Paxillin/HDAC6 signaling pathway regulates microtubule acetylation in electric field-guided keratinocyte migration.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Julia Weikum, Jeroen F. van Dyck, Saranya Subramani, David P. Klebl, Merete Storflor, Stephen P. Muench, Soren Abel, Frank Sobott, J. Preben Morth
Summary: The study reveals the complex interaction between bacterial magnesium transporter A (MgtA) and cardiolipin 18:1 and cardiolipin 16:0, highlighting the importance of lipid environment in protein activity and stability. Further understanding of Mg2+ homeostasis in bacteria will provide insights into bacterial infections.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Sumit Kinger, Yuvraj Anandrao Jagtap, Ankur Rakesh Dubey, Prashant Kumar, Akash Choudhary, Rohan Dhiman, Vijay Kumar Prajapati, Deepak Chitkara, Krishna Mohan Poluri, Amit Mishra
Summary: Efficient protein synthesis and quality control mechanisms are crucial for maintaining proteostasis and preventing neurodegeneration. This study demonstrates that treating cells with Lanosterol can enhance the proteolytic activity of Proteasome and promote the removal of misfolded proteins, suggesting a potential therapeutic approach for abnormal protein accumulation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Karolina Stepien, Adrianna Skoneczna, Monika Kula-Maximenko, Lukasz Jurczyk, Mateusz Molon
Summary: The replication of DNA requires a complex machinery called the replisome, which is highly conserved across species. One crucial component of the replisome is the CMG helicase complex, which unwinds DNA and coordinates the assembly and function of other replisome components. In this study, the impact of the absence of one copy of the CMG complex genes on the physiology and aging of yeast cells was investigated. The findings showed disruptions in the cell cycle, extended doubling times, and alterations in the biochemical profile of these cells. Importantly, it was found that heterozygous cells for CMG helicase genes exhibited increased reproductive potential and delayed aging. The study also highlighted potential therapeutic targets for cancer treatment using yeast.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Nishadh Rathod, Guadalupe Guerrero-Serna, Howard S. Young, L. Michel Espinoza-Fonseca
Summary: This study reveals that replacing Lys27 with Asn enhances the inhibitory potency of MLN without affecting SERCA's affinity for Ca2+. The findings suggest that the SERCA site modulating Ca2+ affinity also functions as a catalytic activity switch.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Can Jiang, Chunyang Zhang, Min Dai, Fuyan Wang, Sa Xu, Dan Han, Yanyan Wang, Yajie Cao, Yanyan Liang, Ziyu Zhang, Lina Yan, Yujun Shen, Kewu He, Yuxian Shen, Jun Liu
Summary: The phosphorylation of p65 and the expression of SUMO1 are increased in cancer tissues of HCC patients, and there is a positive correlation between SUMO1 and phosphorylated p65. SUMOylation of p65 by SUMO1 promotes p65 nuclear import and enhances NF-xB activity. Both SUMOylation and phosphorylation of p65 increase the viability and invasion of hepatoma cells, and decrease cell apoptosis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Ming-Fo Hsu, Yoshihiro Ito, Jai Prakash Singh, Shu-Fang Hsu, Alan Wells, Kuang-Yu Jen, Tzu-Ching Meng, Fawaz G. Haj
Summary: This study identified alpha-actinin4 as a novel substrate of PTP1B in podocytes and demonstrated their interaction in regulating podocyte function. Targeting PTP1B and alpha-actinin4 could be a potential therapeutic approach for podocyte injury.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Paulo F. V. Bizerra, Eduardo H. Gilglioni, Hang Lam Li, Simei Go, Ronald P. J. Oude Elferink, Arthur J. Verhoeven, Jung -Chin Chang
Summary: This study investigates the role of cyclic AMP (cAMP) in glycogen metabolism and reveals that cAMP regulates glycogenolysis in opposite directions depending on its site of synthesis within cells and downstream effectors. The canonical tmAC-cAMP-PKA signaling promotes glycogenolysis, while the non-canonical sAC-cAMP-Epac1 signaling suppresses glycogenolysis. This highlights the importance of cAMP microdomain organization for distinct metabolic regulation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)