Article
Microbiology
Yidong Liu, Wenxuan Sun, Liting Ma, Rong Xu, Chunyu Yang, Ping Xu, Cuiqing Ma, Chao Gao
Summary: Given the intrinsic and potential resistance of Pseudomonas aeruginosa to antibiotics, it is crucial to develop new therapeutic options for infections caused by this bacterium. Bacterial metabolic pathways are being explored as potential targets for new antibiotics. This study investigates the metabolic mechanisms of glycerol and its intermediate glycerol 3-phosphate (G3P) in P. aeruginosa PAO1. The results reveal the importance of G3P homeostasis for the growth and virulence factor production of P. aeruginosa PAO1. The enzyme GlpD, involved in G3P catabolism, is identified as a potential therapeutic target for the prevention and treatment of P. aeruginosa infections.
Article
Biochemistry & Molecular Biology
Kevin Wang, Jonathan Hirschenson, Amanda Moore, Ryan J. Mailloux
Summary: This study found that the glutathionylation of mitochondrial complex I can lead to increased production of ROS during reverse electron transfer from the ubiquinone pool. This has implications for understanding the relationship between mitochondrial glutathionylation reactions and oxidative stress induction in various pathologies.
Article
Biochemistry & Molecular Biology
Soumyajit Mukherjee, Shubhojit Das, Minakshi Bedi, Lavanya Vadupu, Writoban Basu Ball, Alok Ghosh
Summary: Human MPV17 is a mitochondrial inner-membrane channel protein that is linked to tissue-specific mitochondrial DNA depletion syndrome, but its molecular function is still unknown. Knockout of Sym1, the yeast ortholog of MPV17, leads to disrupted mitochondrial morphology and phospholipids composition. Supplementation of methylglyoxal (MG) restores respiratory growth by activating cytosolic NAD-dependent glycerol-3-phosphate dehydrogenase 1 (Gpd1), which restores the levels of mitochondrial phospholipids and respiration. Activation of Gpd1 could be a potential strategy for combating Sym1 deficiency and associated phospholipids defects.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2023)
Article
Endocrinology & Metabolism
Michael J. MacDonald, Israr-ul H. Ansari, Melissa J. Longacre, Scott W. Stoker
Summary: The study reassessed whether metformin inhibits mitochondrial glycerol phosphate dehydrogenase and found that it does not. Additionally, the experiment showed that metformin has beneficial effects even in tissues with high levels of mGPD, contradicting previous assumptions.
Article
Biochemistry & Molecular Biology
Clauber Henrique Souza da Costa, Ted Wilson Bichara, Guelber Cardoso Gomes, Alberto Monteiro dos Santos, Kaue Santana da Costa, Anderson Henrique Lima e Lima, Claudio Nahum Alves, Jeronimo Lameira
Summary: Allosteric changes in enzyme activity are modulated by ligand binding, with implications for drug design. This study focused on analyzing the conformational dynamics of glycerol-3-phosphate dehydrogenase in Leishmania mexicana, providing insights into potential drug discovery targets in the reversible redox conversion pathway.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Jiahui Meng, Chunyu Zhang, Danni Wang, Lu Zhu, Lingdi Wang
Summary: This study reveals a new regulatory mode of GCN5L1 in hepatic gluconeogenesis by modulating lactate and glycerol metabolism. The deletion of GCN5L1 inhibits glucose production derived from lactate and glycerol due to increased cytosolic redox state. GCN5L1 directly binds to the key component of mitochondrial shuttle GPD2 and regulates its activity.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Guy A. Rutter, Vaibhav Sidarala, Brett A. Kaufman, Scott A. Soleimanpour
Summary: The regulation of glucose-regulated insulin secretion in diabetes is defective. This review focuses on the role of glucose's privileged oxidative metabolism in glucose detection, the regulation of mitochondrial metabolism by Ca2+, and the importance of mitochondrial structure and dynamics in beta cells. Additionally, it highlights the contributions of Professor Randle and his colleagues towards our understanding of insulin secretion regulation.
BIOCHEMICAL JOURNAL
(2023)
Article
Agricultural Engineering
Pseudomonas Asiatica, Trinh Thi Nguyen, Suman Lama, Satish Kumar Ainala, Mugesh Sankaranarayanan, Ashish Singh Chauhan, Jung Rae Kim, Sunghoon Park
Summary: The study demonstrates that Pseudomonas asiatica C1 can be a promising host for the production of 3-HP from glycerol by genetic editing and optimization, achieving high production efficiency and molar yield on glucose.
BIORESOURCE TECHNOLOGY
(2021)
Article
Chemistry, Analytical
Jueun Lee, Jin A. Shin, Eun-Mi Lee, Miso Nam, Eun-Mi Park
Summary: Recent studies demonstrate that changes in energy metabolism in activated microglia play a role in their immune responses in the ischemic brain. Noggin, an antagonist of bone morphogenetic protein, has been found to enhance myelination in the ischemic brain, and conditioned media (CM) from activated BV2 microglia treated with noggin can increase the expression of myelin basic protein (MBP) in oligodendrocytes. Metabolite analysis revealed that noggin treatment suppressed the increase in intracellular glucose and lactate levels in BV2 cells after ischemia/reperfusion (I/R), but increased extracellular levels of glucose and several amino acids. In MO3.13 cells, noggin CM reversed changes in metabolite levels induced by vehicle CM, suggesting that noggin-induced metabolic changes in microglia create a favorable environment for myelin synthesis in oligodendrocytes.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Biology
Lisa Bjerregaard Jorgensen, Johannes Overgaard, Florence Hunter-Manseau, Nicolas Pichaud
Summary: The heat tolerance of ectotherms, such as insects, is linked to the failure of oxidative phosphorylation (OXPHOS) and/or ATP production at critically high temperatures, with complex I-supported respiration (CI-OXPHOS) decreasing significantly at higher temperatures but the enzymatic catalytic capacity of complex I remaining intact. Despite the reduction in CI-OXPHOS, all species were able to maintain maximal OXPHOS capacity through oxidation of alternative substrates, indicating important mitochondrial flexibility at temperatures exceeding organismal heat limits. Interestingly, the failure of CI-OXPHOS and compensatory oxidation of alternative substrates occurred at temperatures correlated with species heat tolerance, suggesting a potential link between mitochondrial function and thermal tolerance in ectotherms.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chidozie N. Okoye, Nirmala Chinnappareddy, Don Stevens, Collins Kamunde
Summary: This study investigated the role of mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) in ROS homeostasis in fish under environmental stress. It found that oxidation of G3P drives ROS production from mGPDH and complexes I, II and III, while Cd directly modulates redox sites but not antioxidant defense systems to alter mitochondrial H2O2 emission.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2022)
Article
Genetics & Heredity
Madhulika Rai, Sarah M. Carter, Shefali A. Shefali, Nader H. Mahmoudzadeh, Robert Pepin, Jason M. Tennessen
Summary: The enzyme glycerol-3-phosphate dehydrogenase 1 (GPDH1) plays essential roles in the development and metabolism of Drosophila melanogaster. Depletion of maternal and zygotic pools of GPDH1 affects larval development, lifespan, fat storage, oogenesis, and embryogenesis. Metabolomics analysis further reveals metabolic adaptations in GPDH1 mutants that differ between generations. These findings expand our understanding of GPDH1's functions in early development and provide insights into the survival mechanisms of flies lacking this key enzyme.
G3-GENES GENOMES GENETICS
(2022)
Review
Endocrinology & Metabolism
Sotiria Tavoulari, Denis Lacabanne, Chancievan Thangaratnarajah, Edmund R. S. Kunji
Summary: Citrin deficiency is a globally prevalent mitochondrial disease with three stages: neonatal intrahepatic cholestasis, a mild adaptation stage, and adult citrullinemia. It is caused by the absence or dysfunction of the calcium-regulated mitochondrial aspartate/glutamate carrier 2 (AGC2/SLC25A13), also known as citrin. This deficiency affects the malate-aspartate shuttle, gluconeogenesis, amino acid homeostasis, and the urea cycle.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Agriculture, Multidisciplinary
Minyoung Kim, Jongchan Lee, Lynn Heo, Sang Jun Lee, Sang-Wook Han
Summary: Acidovorax citrulli (Ac) is the causal agent of bacterial fruit blotch in watermelon. A putative glycerol-3-phosphate dehydrogenase in Ac (GlpdAc) was found to play a role in glycerol metabolism, glycolysis, cell aggregation, and virulence. This study expands the understanding of proteins associated with virulence in Ac.
PLANT PATHOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Beatriz Hernandez-Ochoa, Gabriel Navarrete-Vazquez, Rodrigo Aguayo-Ortiz, Paulina Ortiz-Ramirez, Laura Morales-Luna, Victor Martinez-Rosas, Abigail Gonzalez-Valdez, Fernando Gomez-Chavez, Sergio Enriquez-Flores, Carlos Wong-Baeza, Isabel Baeza-Ramirez, Veronica Perez de la Cruz, Saul Gomez-Manzo
Summary: The study identified promising novel drug candidates against H. pylori by testing 55 compounds for inhibitory activity on HpG6PD. These compounds showed inhibition at the NADP(+) catalytic binding site, potentially exerting a competitive inhibitory effect with NADP(+) and a non-competitive or uncompetitive effect with G6P. This suggests that these compounds could be effective in targeting HpG6PD as a treatment for H. pylori infections.
Review
Biochemistry & Molecular Biology
Victoria I. Bunik, Martin D. Brand
BIOLOGICAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Hoi-Shan Wong, Berengere Benoit, Martin D. Brand
FREE RADICAL BIOLOGY AND MEDICINE
(2019)
Review
Biochemistry & Molecular Biology
Mark A. Watson, Hoi-Shan Wong, Martin D. Brand
BIOCHEMICAL SOCIETY TRANSACTIONS
(2019)
Article
Cardiac & Cardiovascular Systems
Kyriakos N. Papanicolaou, Deepthi Ashok, Ting Liu, Tyler M. Bauer, Junhui Sun, Zhen Li, Eduardo Costa, Charles Crepy D'Orleans, Sara Nathan, David J. Lefer, Elizabeth Murphy, Nazareno Paolocci, D. Brian Foster, Brian O'Rourke
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2020)
Article
Cardiac & Cardiovascular Systems
Barbara Roman, Pawandeep Kaur, Deepthi Ashok, Mark Kohr, Roopa Biswas, Brian O'Rourke, Charles Steenbergen, Samarjit Das
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Jingqi Fang, Hoi-Shan Wong, Martin D. Brand
Article
Cardiac & Cardiovascular Systems
Brian O'Rourke, Deepthi Ashok, Ting Liu
Summary: The discovery of mitochondrial Ca2+ influx and efflux pathways has reignited interest in the regulation of mitochondrial Ca2+ balance and its roles in health and disease. Despite advances in cellular and animal models, fundamental questions remain about the regulation and functional impact of mitochondrial Ca2+, particularly in heart failure, which will impact therapeutic approaches.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Article
Biophysics
Deepthi Ashok, Brian O'Rourke
Summary: The researchers developed an analytical workflow called MitoWave, incorporating wavelet transform methods and image segmentation to identify dynamic Delta Psi(m) changes in the cardiac mitochondrial network. In vitro experiments showed that mitochondria exhibit complex oscillatory Delta Psi(m) during ischemia/reperfusion, with MitoWave analysis successfully tracking and quantifying this behavior.
BIOPHYSICAL JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Shona A. Mookerjee, Akos A. Gerencser, Mark A. Watson, Martin D. Brand
Summary: Mitochondrial oxidation of succinate can generate a higher protonmotive force than that of NADH-linked substrates, due to differences in redox potentials. Biological constraints tune the oxidation of NADH and succinate to maintain suitable mitochondrial pmf for cellular needs without causing pathology. Conditions that allow succinate oxidation to drive pmf too high can lead to pathological generation of reactive oxygen species.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Jingqi Fang, Yini Zhang, Akos A. Gerencser, Martin D. Brand
Summary: The effects of substrate addition on cellular hydrogen peroxide release rate and origin depend on whether endogenous substrates are depleted, and increasing hydrogen peroxide release and improving mitochondrial energy state can enhance the release rate.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Kyriakos N. Papanicolaou, Jessica Jung, Deepthi Ashok, Wenxi Zhang, Amir Modaressanavi, Eddie Avila, D. Brian Foster, Natasha E. Zachara, Brian O'Rourke
Summary: O-GlcNAcylation plays a crucial role in regulating the activity of Erk1/2 and p38 MAPKs, thus affecting the signaling pathways involved in hypertrophic growth responses in cardiomyocytes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Edwin T. Gibbs II, Chad A. Lerner, Mark A. Watson, Hoi-Shan Wong, Akos A. Gerencser, Martin D. Brand
Summary: Superoxide/hydrogen peroxide production by site IQ in complex I occurs during both reverse and forward electron transport, and is equally sensitive to S1QELs, rotenone, and piericidin A. A new assay is introduced to determine the direction of electron flow through complex I. The results show that superoxide/hydrogen peroxide production by site IQ in cells is S1QEL-sensitive and occurs during forward electron transport.
BIOCHEMICAL JOURNAL
(2023)
Article
Endocrinology & Metabolism
David G. Nicholls, Martin D. Brand
Summary: Brown adipose tissue is specialized for thermogenesis, with active mitochondrial electron transport chain and unique uncoupling protein UCP1. Its presence in humans may contribute to diet-induced thermogenesis and protect cardio-metabolic health. Manipulation of creatine metabolism can influence diet- and cold-induced metabolism, but the evidence for a significant futile creatine cycle in these tissues is currently lacking.
Article
Medicine, Research & Experimental
Sumita Mishra, Nandhini Sadagopan, Brittany Dunkerly-Eyring, Susana Rodriguez, Dylan C. Sarver, Ryan P. Ceddia, Sean A. Murphy, Hildur Knutsdottir, Vivek P. Jani, Deepthi Ashok, Christian U. Oeing, Brian O'Rourke, Jon A. Gangoiti, Dorothy D. Sears, G. William Wong, Sheila Collins, David A. Kass
Summary: Inhibition of PDE9 shows promising effects in improving obesity and cardiometabolic syndrome symptoms, especially in male and ovariectomized female mice. PDE9-I stimulates mitochondrial activity in brown and white fat, reduces various fat deposits, and improves CMS without significantly affecting activity or food intake.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Biochemistry & Molecular Biology
Martin D. Brand
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2020)