Article
Plant Sciences
Mohammed M. Mira, Robert D. Hill, Alexander Hilo, Matthias Langer, Sean Robertson, Abir U. Igamberdiev, Olivia Wilkins, Hardy Rolletschek, Claudio Stasolla
Summary: Preservation of stem cell functionality during hypoxia is achieved through the activation of the TCA cycle and the retention of starch and carbohydrates by phytoglobin. Maize QC stem cells, despite being highly hypoxic under normal oxygen tension, are vulnerable to hypoxic stress and show impairment in various metabolic processes. Overexpression of PHYTOGLOBIN 1 preserves the functionality of QC stem cells during stress by rewiring their metabolism.
Article
Geriatrics & Gerontology
P. La Padula, L. E. Costa, A. Karadayian, S. Lores-Arnaiz, A. Czerniczyniec
Summary: In old rats, acute hypobaric hypoxia leads to different responses in brain and heart mitochondria. The brain mitochondria show mild uncoupling and increased NO production, while the heart mitochondria decrease ROS production and NO production through increased cytochrome oxidase activity, suggesting a self-protective mechanism.
EXPERIMENTAL GERONTOLOGY
(2023)
Article
Environmental Sciences
Xiaozheng Zhu, Yikai Shou, Xintong Ji, Yu Hu, Huanhuan Wang
Summary: Exposure to PM2.5 can lead to neuronal apoptosis, which is a key event in air pollution-induced neurodegenerative diseases. AMD1 and spermidine are associated with neuronal apoptosis induced by PM2.5 exposure, with a mechanism at least partially dependent on the mitochondria-mediated pathway.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Biochemistry & Molecular Biology
Divya Seth, Colin T. Stomberski, Precious J. McLaughlin, Richard T. Premont, Kathleen Lundberg, Jonathan S. Stamler
Summary: The aim of this study was to investigate the interactions between nitric oxide synthase (NOS) isoforms and proteins, as well as the mechanisms by which they mediate S-nitrosylation. The results showed that each NOS isoform interacts with and S-nitrosylates many proteins, but a large proportion of S-nitrosylated proteins are not associated with NOS. Additionally, the interactomes and S-nitrosylomes of individual NOS isoforms are largely unique, indicating specific roles for each isoform in S-nitrosylation.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Chemistry, Physical
Mengyu Sun, Yanjuan Sang, Qingqing Deng, Zhengwei Liu, Jinsong Ren, Xiaogang Qu
Summary: A nanozyme-based NO generator, cerium oxide (CeO2)-AT, has been developed to selectively produce nitric oxide (NO) in cancer cells for tumor treatment. The generator can disrupt the mitochondrial respiratory chain of tumor cells and induce cell apoptosis by catalyzing the production of NO in the mitochondria of cancer cells. Furthermore, the generator can improve the performance of NO gas therapy by catalyzing H2O2 to produce O-2. This study provides a new approach for safe and specific cancer therapy using highly selective NO-based treatment.
Article
Endocrinology & Metabolism
Ryan L. Hoiland, David B. MacLeod, Benjamin S. Stacey, Hannah G. Caldwell, Connor A. Howe, Daniela Nowak-Fluck, Jay M. J. R. Carr, Michael M. Tymko, Geoff B. Coombs, Alexander Patrician, Joshua C. Tremblay, Michelle Van Mierlo, Chris Gasho, Mike Stembridge, Mypinder S. Sekhon, Damian M. Bailey, Philip N. Ainslie
Summary: Through four investigations, it was found that cerebral hypoxic vasodilation is associated with nitric oxide and hemoglobin-based signaling. The release of S-nitrosothiol (RSNO) through trans-cerebral pathways is correlated to cerebral hypoxic vasodilation, while nitrite (NO2-) is not. Inhibition of nitric oxide synthase reduces cerebral hypoxic vasodilation. Among high-altitude native Andeans with excessive erythrocytosis, cerebral hypoxic vasodilation is inversely correlated with hemoglobin concentration and can be improved with hemodilution.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Article
Chemistry, Multidisciplinary
Xiao Fang, Shuxian Cai, Min Wang, Zhaowei Chen, Chunhua Lu, Huanghao Yang
Summary: The study introduces a NO-based phototherapeutic strategy for hypoxic tumors using photogenerated holes to oxidize water into H2O2, subsequently producing NO. In vitro and in vivo experiments demonstrated that this strategy induced cancer cell apoptosis, paving the way for the development of NO therapeutic strategies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Adelheid Weidinger, Nadja Milivojev, Arthur Hosmann, J. Catharina Duvigneau, Csaba Szabo, Gabor Toro, Laurin Rauter, Annette Vaglio-Garro, V. Garik Mkrtchyan, Lidia Trofimova, Rinat R. Sharipov, Alexander M. Surin, Irina A. Krasilnikova, Vsevolod G. Pinelis, Laszlo Tretter, Rudolf Moldzio, Hulya Bayir, Valerian E. Kagan, Victoria I. Bunikg, Andrey V. Kozlov
Summary: Brain injury leads to neuroinflammation, extracellular glutamate accumulation, and mitochondrial dysfunction, causing neuronal death. This study aimed to investigate the effects of these mechanisms on neuronal death. Patients with aneurysmal subarachnoid hemorrhage (SAH) were recruited from a neurosurgical intensive care unit, and in vitro experiments were performed using rat cortex homogenate, neuronal cultures, and cell lines. The results showed that elevated levels of extracellular glutamate and nitric oxide (NO) metabolites were associated with poor clinical outcome in SAH patients. Inhibition of the key enzyme OGDHC from the glutamate-dependent segment of the tricarboxylic acid cycle by NO led to extracellular glutamate accumulation and neuronal death. However, reactivation of OGDHC by its cofactor thiamine reduced extracellular glutamate levels and protected against glutamate toxicity.
Article
Chemistry, Applied
Chang Liu, Qihang Gao, Zhen Zeng, Huan Ding, Huirong Yao, Song He, Liancheng Zhao, Xianshun Zeng
Summary: We reported a novel mitochondria-targeted fluorescent dye DTPO with deep-red emission wavelength and improved Stokes shift, which shows great potential in biological imaging applications. The dye exhibits excellent properties such as high molar extinction coefficients, large fluorescence quantum yields, tolerance to photobleaching, low toxicity to living cells, and accumulation in mitochondria.
Article
Pharmacology & Pharmacy
Christian Arias-Reyes, Sofien Laouafa, Natalia Zubieta-DeUrioste, Vincent Joseph, Aida Bairam, Edith M. Schneider Gasser, Jorge Soliz
Summary: The study reveals that EPO stimulates CSN activity under hypoxic conditions at lower concentrations, but inhibits it at higher concentrations. The inhibitory effect of high-dose EPO on CSN activity may be attributed to an increase in nitric oxide production.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Estefania Caballano-Infantes, Irene Diaz, Ana Belen Hitos, Gladys Margot Cahuana, Antonio Martinez-Ruiz, Barbara Soria-Juan, Rosario Rodriguez-Grinolo, Abdelkrim Hmadcha, Franz Martin, Bernat Soria, Juan R. Tejedo, Francisco Javier Bedoya
Summary: The study demonstrates that NO can mimic hypoxia response in human PSCs under normoxic conditions, enhancing their stemness properties and altering their metabolic profile, including upregulation of genes like HIF-1 alpha, HIF-2 alpha, NANOG, OCT-4, and increased expression of glycolysis and mitochondrial fusion regulators.
Article
Oncology
Rafael Mena-Osuna, Ana Mantrana, Silvia Guil-Luna, Maria Teresa Sanchez-Montero, Carmen Navarrete-Sirvent, Teresa Morales-Ruiz, Aurora Rivas-Crespo, Marta Toledano-Fonseca, Maria Victoria Garcia-Ortiz, Gema Garcia-Jurado, Maria Auxiliadora Gomez-Espana, Rafael Gonzalez-Fernandez, Carlos Villar, Francisco Javier Medina-Fernandez, Jose Manuel Villalba, Enrique Aranda, Antonio Rodriguez-Ariza
Summary: In this study, the researchers found that the deficiency of S-nitrosoglutathione reductase (GSNOR) in tumors is associated with poor prognostic features and survival in patients with colorectal cancer. GSNOR-low tumors exhibit an immunosuppressive microenvironment and altered energy metabolism characterized by impaired oxidative phosphorylation and reliance on glycolysis. The results suggest that GSNOR deficiency promotes tumor progression through immune evasion and metabolic reprogramming in CRC.
JOURNAL OF PATHOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Arbindra Timilsina, Wenxu Dong, Mirza Hasanuzzaman, Binbin Liu, Chunsheng Hu
Summary: Plant survival and adaptation during oxygen deprivation, caused by various biotic and abiotic factors, rely on mechanisms such as fermentation, antioxidant enzymes, and the reduction pathways of nitrate and nitric oxide. Understanding the molecular mechanisms involved in reducing nitric oxide toxicity is important not only for plant physiology, but also for addressing uncertainties in the global nitrous oxide budget.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Physiology
Ruiqin Hu, Genfang Li, Qianghua Xu, Liangbiao Chen
Summary: This study investigated the role of iron in the hypoxic responses of two zebrafish-derived cell lines. The results showed that iron homeostasis is important for maintaining mitochondrial integrity in hypoxic stress, and this effect is cell type-dependent.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Kapuganti Jagadis Gupta, Vemula Chandra Kaladhar, Teresa B. Fitzpatrick, Alisdair R. Fernie, Ian Max Moller, Gary J. Loake
Summary: Nitric oxide (NO) is an important signal molecule in plants, playing key roles in plant development and stress responses. This review focuses on the pathways involved in NO production and scavenging, and how they are integrated with cellular metabolism.
Article
Biochemistry & Molecular Biology
Danchen Wu, Asish Dasgupta, Austin D. Read, Rachel E. T. Bentley, Mehras Motamed, Kuang-Hueih Chen, Ruaa Al-Qazazi, Jeffrey D. Mewburn, Kimberly J. Dunham-Snary, Elahe Alizadeh, Lian Tian, Stephen L. Archer
Summary: This article discusses the important role of the homeostatic oxygen sensing system (HOSS) in regulating oxygen delivery, as well as the mechanisms of pseudohypoxia that may occur in diseases such as pulmonary arterial hypertension (PAH) and cancer.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemical Research Methods
Kanawat Wiwatchaitawee, Kareem Ebeid, Juliana C. Quarterman, Youssef Naguib, Md Yousuf Ali, Claudia Oliva, Corinne Griguer, Aliasger K. Salem
Summary: In this study, loading paclitaxel (PTX) into a polymeric, nanoparticulate delivery system improved its accumulation and therapeutic activity in the brain. By incorporating positively charged surface modifiers onto polymeric nanoparticles, significant improvement in brain accumulation was achieved. The efficacy of PTX-loaded nanoparticles with a specific surface modifier was demonstrated in a mouse model of GBM, showing improved survival and equivalent safety compared to soluble PTX.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Kimberly J. Dunham-Snary, Bas G. J. Surewaard, Jeffrey D. Mewburn, Rachel E. T. Bentley, Ashley Y. Martin, Oliver Jones, Ruaa Al-Qazazi, Patricia A. D. Lima, Paul Kubes, Stephen L. Archer
Summary: Mitochondria in human neutrophils play a critical role in the killing of Staphylococcus aureus. They contribute to bacterial clearance through mechanisms such as phagocytosis and vital NETosis.
Article
Multidisciplinary Sciences
Rachel E. T. Bentley, Charles C. T. Hindmarch, Kimberly J. Dunham-Snary, Brooke Snetsinger, Jeffrey D. Mewburn, Arthur Thebaud, Patricia D. A. Lima, Bernard Thebaud, Stephen L. Archer
Summary: In this study, human DA smooth muscle cells (DASMCs) were studied to understand their functional and transcriptomic changes under different oxygen conditions. Results showed that exposure to oxygen induced an increase in intracellular calcium and muscle constriction in these cells, and they demonstrated responsiveness to different oxygen conditions.
Article
Biochemistry & Molecular Biology
Md Yousuf Ali, Claudia R. Oliva, Susanne Flor, Prabhat C. Goswami, Corinne E. Griguer
Summary: This study identified the molecular mechanism of radioresistance in glioblastoma (GBM) as changes in the cellular labile iron pool (LIP) and the activity of cytochrome c oxidase (CcO). By manipulating CcO and LIP, the sensitivity of radioresistant GBM cells to radiation may be restored.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Review
Cell Biology
Md Yousuf Ali, Claudia R. Oliva, Susanne Flor, Corinne E. Griguer
Summary: Iron is crucial for cellular processes, but maintaining iron homeostasis is essential for balanced cellular signaling and disease prevention. Mitoferrins, as the principal iron importers in human cell mitochondria, play a critical role in maintaining cytosolic and mitochondrial iron homeostasis.
Article
Biochemistry & Molecular Biology
Claudia R. Oliva, Md Yousuf Ali, Susanne Flor, Corinne E. Griguer
Summary: This study explores how different isoforms of COX4 affect glioma metabolism. COX4-1 overexpression is associated with upregulated purine and glutathione metabolism, while downregulating glycolysis and fatty acid metabolism.
Article
Biochemistry & Molecular Biology
Stephen L. Archer, Asish Dasgupta, Kuang-Hueih Chen, Danchen Wu, Kaushal Baid, John E. Mamatis, Victoria Gonzalez, Austin Read, Rachel ET. Bentley, Ashley Y. Martin, Jeffrey D. Mewburn, Kimberly J. Dunham-Snary, Gerald A. Evans, Gary Levy, Oliver Jones, Ruaa Al-Qazazi, Brooke Ring, Elahe Alizadeh, Charles CT. Hindmarch, Jenna Rossi, Patricia DA. Lima, Darryl Falzarano, Arinjay Banerjee, Che C. Colpitts
Summary: This study demonstrates that SARS-CoV-2 causes apoptosis and mitochondrial dysfunction in airway epithelial cells, leading to impaired bioenergetics and hypoxemia. The virus also suppresses hypoxic pulmonary vasoconstriction by targeting mitochondria. These findings highlight the importance of mitochondrial pathology in COVID-19 pneumonia and suggest it as a potential therapeutic target.
Review
Endocrinology & Metabolism
Emily Mason, Charles C. T. Hindmarch, Kimberly J. Dunham-Snary
Summary: MCADD is a common inherited metabolic disorder that can have serious health implications, especially in children. Accurate diagnosis and proper intervention can successfully manage this disease.
ENDOCRINOLOGY DIABETES & METABOLISM
(2023)
Review
Endocrinology & Metabolism
Mia S. Wilkinson, Kimberly J. Dunham-Snary
Summary: Mitochondria play important regulatory roles in cellular metabolism and damaged/dysfunctional mitochondria are major contributors to many common human diseases. Peripheral blood cells, especially platelets, are being investigated as an ideal candidate for assessing mitochondrial function due to accessibility and documented pathology-related dysfunction. Platelet mitochondrial bioenergetics are being studied in various diseases and physiological states, with early findings supporting their use as a biomarker for mitochondrial functional health.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Cardiac & Cardiovascular Systems
Austin D. Read, Rachel E. T. Bentley, Ashley Y. Martin, Jeffrey D. Mewburn, Elahe Alizadeh, Danchen Wu, Patricia D. A. Lima, Kimberly J. Dunham-Snary, Bernard Thebaud, Willard Sharp, Stephen L. Archer
Summary: Upon the first breath, the ductus arteriosus (DA) constricts in response to increased partial pressure of oxygen (pO(2)), diverting blood flow to the pulmonary circulation. This study identified that the DA's oxygen sensor relies on pO(2)-dependent changes in electron leak at site I-Q in the mitochondrial electron transport chain, independently of metabolism. By inhibiting electron leak, the electron leak suppressor S1QEL effectively prevented O-2-induced rises in ROS and DA constriction both ex vivo and in vivo. These findings suggest that S1QEL offers a therapeutic means to maintain DA patency.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Oncology
Corinne E. Griguer, Claudia R. Oliva, Christopher S. Coffey, Merit E. Cudkowicz, Robin A. Conwit, Anna L. Gudjonsdottir, Dixie J. Ecklund, Janel K. Fedler, Tina M. Neill-Hudson, Louis B. Nabors, Melanie Benge, James R. Hackney, Marianne Chase, Timothy P. Leonard, Toral Patel, Howard Colman, Macarena de la Fuente, Rekha Chaudhary, Karen Marder, Teri Kreisl, Nimish Mohile, Milan G. Chheda, Katharine McNeill, Priya Kumthekar, Aclan Dogan, Jan Drappatz, Vinay Puduvalli, Agnes Kowalska, Jerome Graber, Elizabeth Gerstner, Stephen Clark, Michael Salacz, James Markert
Summary: Through a prospective study of 152 newly diagnosed GBM patients, it was found that tumor CcO activity alone is not a prognostic marker for GBM patients. However, the combination of low CcO activity and methylated MGMT promoter may indicate improved long-term survival in a subgroup of GBM patients, which warrants further investigation.
NEURO-ONCOLOGY ADVANCES
(2022)
Article
Cell Biology
Claudia R. Oliva, Md Yousuf Ali, Susanne Flor, Corinne E. Griguer
Summary: In this study, the authors found that acquired radioresistance in glioblastoma (GBM) is associated with metabolic changes characterized by increased activity of CcO and a switch in COX4 isoform expression. They also demonstrated that COX4-1 promotes the assembly of SCs in GBM cells and may regulate the production of reactive oxygen species, thus contributing to radioresistance.
