Article
Biochemistry & Molecular Biology
Cheuk Hei Ho, Chiara Paolantoni, Praveen Bawankar, Zuojian Tang, Stuart Brown, Jean-Yves Roignant, Jessica E. Treisman
Summary: The exon junction complex regulates various functions related to mRNA splicing, translation, degradation, and localization, with Barentsz playing a distinct role in Drosophila neuromuscular development. Barentsz is involved in mitochondrial distribution and synapse growth, independent of its interactions with the exon junction complex. Additionally, Barentsz influences synapse growth through the regulation of Activin ligand Dawdle expression.
Article
Neurosciences
Kiel G. Ormerod, Anthony E. Scibelli, J. Troy Littleton
Summary: The Drosophila neuromuscular system has been used to study synaptic development and function, but little is known about specific synaptic alterations on neuromuscular transduction and muscle contractility. Studies show that larval muscle contraction force increases with motoneuron stimulation frequency and duration, with plasticity between 5 and 40 Hz. Genetic and pharmacological manipulations of Ca2+ regulation components affect muscle contraction strength and timing. Identification of a FMRFa peptide and its signaling pathway dramatically improves muscle performance, showcasing Drosophila as a model for studying excitation-contraction coupling.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Biochemistry & Molecular Biology
Cristina Pinto, Viviana Perez, Jessica Mella, Miguel Albistur, Teresa Caprile, Francisca C. Bronfman, Juan Pablo Henriquez
Summary: The study demonstrates that Wnt3 is transported and secreted by motor neurons to induce postsynaptic differentiation in nascent NMJs. Overexpression of Wnt3 in NSC-34 cells effectively induces acetylcholine receptor clustering on co-cultured myotubes.
Article
Biochemistry & Molecular Biology
Jacob L. Brown, Fredrick F. Peelor, Constantin Georgescu, Jonathan D. Wren, Michael Kinter, Victoria J. Tyrrell, Valerie B. O'Donnell, Benjamin F. Miller, Holly Van Remmen
Summary: Loss of innervation is a major factor contributing to muscle atrophy and weakness. Lipid hydroperoxides and oxylipins play a crucial role in denervation-induced atrophy by regulating mitochondrial hydroperoxide generation and fatty acid metabolism, leading to increased protein breakdown and muscle loss. Treatment with a lipid hydroperoxide scavenger can reduce the generation of mitochondrial hydroperoxides and oxylipins, protecting muscle mass and fiber cross sectional area.
Article
Biochemistry & Molecular Biology
James H. Schofield, Zachary T. Schafer
Summary: The relationship between mitophagy and ROS production is complex and not fully understood. This review discusses mtROS generation and their detrimental effects on cellular viability, along with the cellular defense mechanisms against oxidative stress. Furthermore, the prominent mechanisms governing mitophagy induction that bear on oxidative stress are explored.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Nutrition & Dietetics
Satoshi Sugita, Kotaro Tamura, Michiko Yano, Yoshihiko Minegishi, Noriyasu Ota
Summary: Study shows that dietary milk fat globule membrane (MFGM) combined with exercise can effectively suppress the progression of age-related neuromuscular junction (NMJ) alterations in old age, even after changes in NMJs have already occurred. The effects also extend to the structure and function of peripheral nerves.
Review
Immunology
Miranda D. Chavez, Hubert M. Tse
Summary: Mitochondrial dysfunction and oxidative stress are associated with T cell-mediated autoimmune diseases, and targeting metabolic pathways can inhibit autoreactive T cell activation. Increasing the requirements of Tregs for ROS and oxidative phosphorylation can promote self-tolerance and inhibit the activity of autoreactive T cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biology
Diego Zelada, Francisca Bermedo-Garcia, Nicolas Collao, Juan P. Henriquez
Summary: Successful regeneration of the neuromuscular junction relies on two fundamental steps: proper arrival of regenerating axons to muscle domains and resilience of postsynaptic domains in morphological and functional terms.
BIOLOGICAL REVIEWS
(2021)
Article
Neurosciences
Kaikai He, Yifu Han, Xiling Li, Roberto X. Hernandez, Danielle Riboul, Touhid Feghhi, Karlis A. Justs, Olena Mahneva, Sarah Perry, Gregory T. Macleod, Dion Dickman
Summary: Neurons exhibit functional diversity and can be classified into tonic or phasic patterns of activity. The synaptic differences between tonic and phasic neurons have remained unclear, but this study found major distinctions in neurotransmitter release properties, Ca2+ influx, and synaptic vesicle coupling between these two types of neurons. The organization and stoichiometry of voltage-gated Ca2+ channels at phasic neuron release sites were also observed to be different. These findings suggest that active zone nano-architecture and Ca2+ influx contribute to differential glutamate release at tonic and phasic synapses.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Ryan J. Durbin, Dante J. Heredia, Thomas W. Gould, Robert B. Renden
Summary: Neurotransmission is influenced by extracellular pH. Alkalization enhances transmitter release and receptor activation, while acidification inhibits these processes and can activate acid-sensitive conductances in the synaptic cleft. The direction of change differs across synapse types. At the mammalian neuromuscular junction (NMJ), the direction and magnitude of pH transients in the synaptic cleft during transmission remain unclear. In this study, researchers investigated the extracellular pH transients at the cholinergic synapse of the mouse NMJ under near physiological conditions and identified their sources. They found that activity-induced intracellular Ca2+ release in the muscle plays a role in cleft alkalization, whereas PMCA inhibition decreases alkalization. This suggests that cholinergic synapses at the mouse NMJ typically alkalize due to cytosolic Ca2+ liberation during activity, unless under highly strenuous conditions where acidification predominates.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Andrew P. Bischer, Timothy M. Baran, Andrew P. Wojtovich
Summary: Environmental surveillance-mediated behavior in Caenorhabditis elegans integrates multiple cues and is coordinated by neurons through signaling cascades. Despite lacking eyes, C. elegans is able to perceive and react to the color blue. This study explains this color perception by showing that internally-generated reactive oxygen species (ROS), in response to light, add to exogenous sources of ROS. Multiple sub-threshold sources of ROS are integrated to coordinate behavioral responses with internal cues. Blue light affects C. elegans behavior through ROS generation by endogenous flavins, mediated by the neuronal gustatory photoreceptor like protein, LITE-1. Overall, this study demonstrates that ROS and LITE-1 play central roles in C. elegans foraging behavior through integration of multiple inputs, including light.
Article
Immunology
Nan-Nan Liang, Ying Zhao, Yue-Yue Guo, Zhi-Hui Zhang, Lan Gao, De-Xin Yu, De-Xiang Xu, Shen Xu
Summary: This study found that mitochondria-derived reactive oxygen species (ROS) contribute to renal cell ferroptosis during lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Inhibition of ferroptosis and scavenging of mitochondrial ROS with specific inhibitors, ferrostatin-1 and MitoQ, respectively, attenuated renal lipid peroxidation, ferroptosis-characteristic mitochondrial damage, and renal cell death. These findings suggest that mitochondria-targeted antioxidants may be potential therapeutic agents for sepsis-induced AKI.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Andrey Y. Vinokurov, Olga A. Stelmashuk, Polina A. Ukolova, Evgeny A. Zherebtsov, Andrey Y. Abramov
Summary: The brain produces various reactive oxygen species at different rates in different brain regions, with the brain stem and cerebellum being more sensitive to oxidative stress. Mitochondrial ROS has minor implications to total ROS production, and levels of lipid peroxidation and GSH vary across brain regions.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Cell Biology
Irene Sanchez-Mirasierra, Sergio Hernandez-Diaz, Saurav Ghimire, Carla Montecinos-Oliva, Sandra-Fausia Soukup
Summary: This article introduces two ImageJ/Fiji automated macros for analyzing synaptic autophagy and exosome release from 2D confocal images, revealing their important roles in neurobiology. The tools Autophagoquant and Exoquant can assist researchers in unbiased, standardized, and rapid analysis of autophagy and exosomal release in the Drosophila NMJ.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Kaela O'Connor, Sally Spendiff, Hanns Lochmueller, Rita Horvath
Summary: Congenital myasthenic syndromes (CMS) are rare neuromuscular disorders that commonly present in childhood or infancy. Recently, mitochondrial genes SLC25A1 and TEFM have been found in patients with suspected CMS, suggesting a potential role of mitochondria in neuromuscular transmission. This review highlights the significant involvement of mitochondria at both the pre- and postsynapse, proposing a new subcategorization of CMS-mitochondrial CMS. Additionally, targeting the neuromuscular transmission in mitochondrial disease could potentially improve patient outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
David J. Muggeridge, Daniel R. Crabtree, Ahmet Tuncay, Ian L. Megson, Gareth Davison, James N. Cobley
Summary: New readily accessible systemic redox biomarkers are needed to understand the biological roles reactive oxygen species (ROS) play in humans. The study used a maximal exercise bout to disrupt redox homeostasis and determine a candidate systemic redox biomarker in human erythrocytes. The results showed that the oxidation level of a specific phosphatase decreased during exercise, and the activity of the phosphatase was greater at rest compared to exercise.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Cell Biology
Helmut Sies, Vsevolod V. Belousov, Navdeep S. Chandel, Michael J. Davies, Dean P. Jones, Giovanni E. Mann, Michael P. Murphy, Masayuki Yamamoto, Christine Winterbourn
Summary: This article discusses the key issues associated with identifying the physiological roles of oxidants, with a focus on H2O2 and O-2(.-). The article emphasizes the need for more precise measurement of oxidants and specific identification of their signaling targets. It also highlights the importance of inter-organellar communication and the contribution of environmental exposures. Development of tools for real-time detection and quantification of individual oxidants is crucial for achieving these goals.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Michael P. Murphy, Edward T. Chouchani
Summary: Succinate, as a signaling modulator, plays multiple roles in biology due to its ability to reflect the redox state of the CoQ pool. Its equilibrium with the CoQ pool enables the communication of the mitochondrial status to the rest of the cell and other cells, explaining the emerging roles of succinate in biology.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Maria Luisa Fiorello, Andrew T. Treweeke, David P. Macfarlane, Ian L. Megson
Summary: Research shows that even low levels of fructose intake can significantly decrease nitric oxide production in endothelial cells and increase metabolic activity, while glucose alone does not have a metabolic impact. Endothelial cells are highly sensitive to circulating fructose, which could have significant implications for the development of atherosclerotic disease associated with high fructose consumption.
Article
Oncology
Tania Capeloa, Joanna Krzystyniak, Donatienne D'Hose, Amanda Canas Rodriguez, Valery L. Payen, Luca X. Zampieri, Justine A. Van de Velde, Zohra Benyahia, Erica Pranzini, Thibaut Vazeille, Maude Fransolet, Caroline Bouzin, Davide Brusa, Carine Michiels, Bernard Gallez, Michael P. Murphy, Paolo E. Porporato, Pierre Sonveaux
Summary: This study investigates the potential of the mitochondria-targeted antioxidant MitoQ in inhibiting breast cancer metastasis. Using human breast cancer cells as models, the researchers demonstrate that MitoQ can inhibit cancer cell migration, invasion, clonogenicity, sphere formation, and spheroid stability. The findings of this study are important for future clinical research and evaluation of MitoQ for the prevention of breast cancer metastasis.
Article
Oncology
Tania Capeloa, Joanna Krzystyniak, Amanda Canas Rodriguez, Valery L. Payen, Luca X. Zampieri, Erica Pranzini, Francoise Derouane, Thibaut Vazeille, Caroline Bouzin, Francois P. Duhoux, Michael P. Murphy, Paolo E. Porporato, Pierre Sonveaux
Summary: Entry into the metastatic phase is devastating for cancer patients. Clinical studies have found that the mitochondria-targeted antioxidant MitoQ can prevent breast cancer metastasis and recurrence.
Article
Biochemistry & Molecular Biology
Fay M. Allen, Ana S. H. Costa, Anja Gruszczyk, Georgina R. Bates, Hiran A. Prag, Efterpi Nikitopoulou, Carlo Viscomi, Christian Frezza, Andrew M. James, Michael P. Murphy
Summary: The study developed a rapid fractionation procedure to stabilize the distribution of metabolites between mitochondria and the cytosol. The procedure revealed the compartmentation of mitochondrial metabolites in vivo and allows for the assessment of metabolite distribution between the cytosol and mitochondria in various situations.
Article
Cell Biology
Catherine A. Bellissimo, Luca J. Delfinis, Meghan C. Hughes, Patrick C. Turnbull, Shivam Gandhi, Sara N. DiBenedetto, Fasih A. Rahman, Peyman Tadi, Christina A. Amaral, Ali Dehghani, James N. Cobley, Joe Quadrilatero, Uwe Schlattner, Christopher G. R. Perry
Summary: This study aimed to determine whether the prospective mitochondrial-enhancing compound Olesoxime can prevent early-stage mitochondrial stress in limb and respiratory muscle from D2.mdx mice. Results showed that Olesoxime selectively preserved or maintained muscle sensitivity to creatine, reduced creatine kinase release, and improved some indices of muscle quality.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
James N. Cobley
Summary: A protein molecule with cysteine residues can have multiple unique protein forms called oxiforms, which are determined by different oxidation-chemotype specifications. The diversity of oxiforms within the human body provides a biological basis for redox heterogeneity, and these oxiforms may enable cells to respond to a broad spectrum of stimuli. However, the biological significance of protein-specific oxiforms remains speculative and requires further exploration through new techniques for quantifying oxiforms, which can advance our understanding of redox regulation in health and disease.
Article
Biochemistry & Molecular Biology
Shinpei Uno, Alexander H. Harkiss, Roy Chowdhury, Stuart T. Caldwell, Tracy A. Prime, Andrew M. James, Brendan Gallagher, Julien Prudent, Richard C. Hartley, Michael P. Murphy
Summary: The targeting of bioactive molecules and probes to mitochondria can be achieved by coupling to the lipophilic triphenyl phosphonium (TPP) cation, which accumulates within mitochondria in response to the mitochondrial membrane potential. In this study, we investigated the effects of using a polyethylene glycol (PEG) linker instead of a simple alkane linker to enhance the water solubility of mitochondria-targeted compounds. We found that the use of PEG greatly improved the uptake of compounds by mitochondria and reduced adsorption to the mitochondrial inner membrane.
Article
Biochemistry & Molecular Biology
Ahmet Tuncay, Daniel R. Crabtree, David J. Muggeridge, Holger Husi, James N. Cobley
Summary: The antibody-linked oxi-state assay (ALISA) is a useful tool for quantifying target-specific cysteine oxidation. It benefits both specialists and non-specialists, with its time-efficient analysis and high-throughput capacities. However, more benchmarking is needed before it can be widely adopted.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
James N. Cobley
Summary: This paper proposes a novel hypothesis that different states of oxidative stress are associated with distinct patterns of cysteine oxidation. Measuring and manipulating these patterns offer promising avenues for advancing oxidative stress research.
Letter
Multidisciplinary Sciences
Valerie B. O'Donnell, Nils H. Schebb, Ginger L. Milne, Michael P. Murphy, Christopher P. Thomas, Dieter Steinhilber, Stacy L. Gelhaus, Hartmut Kuehn, Michael H. Gelb, Per-Johan Jakobsson, Ian A. Blair, Robert C. Murphy, Bruce A. Freeman, Alan R. Brash, Garret A. Fitzgerald
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Andrew M. James, Abigail A. I. Norman, Jack W. Houghton, Hiran A. Prag, Angela Logan, Robin Antrobus, Richard C. Hartley, Michael P. Murphy
Summary: A new mass spectrometry probe, CysTPP, has been developed to sensitively detect major acyl-CoAs in rat tissues, revealing the potential importance of longer-chain fatty acyl-CoAs in modifying protein residues non-enzymatically.
CELL CHEMICAL BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Michael P. Murphy, Hulya Bayir, Vsevolod Belousov, Christopher J. Chang, Kelvin J. A. Davies, Michael J. Davies, Tobias P. Dick, Toren Finkel, Henry J. Forman, Yvonne Janssen-Heininger, David Gems, Valerian E. Kagan, Balaraman Kalyanaraman, Nils-Goran Larsson, Ginger L. Milne, Thomas Nystrom, Henrik E. Poulsen, Rafael Radi, Holly Van Remmen, Paul T. Schumacker, Paul J. Thornalley, Shinya Toyokuni, Christine C. Winterbourn, Huiyong Yin, Barry Halliwell
Summary: This article discusses the important roles of reactive oxygen species (ROS) in health and disease, and proposes guidelines and best practices for the nomenclature and assessment of ROS, oxidative reactions, and oxidative damage in cells, tissues, and in vivo.