Article
Biochemistry & Molecular Biology
Barbara Elsnicova, Daniela Hornikova, Veronika Tibenska, David Kolar, Tereza Tlapakova, Benjamin Schmid, Markus Mallek, Britta Eggers, Ursula Schloetzer-Schrehardt, Viktoriya Peeva, Carolin Berwanger, Bettina Eberhard, Hacer Durmus, Dorothea Schultheis, Christian Holtzhausen, Karin Schork, Katrin Marcus, Jens Jordan, Thomas Luecke, Peter F. M. van der Ven, Rolf Schroeder, Christoph S. Clemen, Jitka M. Zurmanova
Summary: Desmin mutations cause cardiomyopathies and negatively impact mitochondria. The deficiency of desmin results in impaired oxidative phosphorylation and fatty and amino acid metabolism in cardiac mitochondria. Increased glucose utilization and upregulation of fetal creatine kinase are compensatory mechanisms to maintain myocardial energy supply.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Rodrigo G. Mira, Waldo Cerpa
Summary: Glutamate, as a major excitatory neurotransmitter in the brain, is involved in synaptic plasticity and excitotoxicity through NMDAR receptors. Mitochondria also play a crucial role in calcium homeostasis, and disruption of this homeostasis can lead to neuronal death.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2021)
Article
Cell Biology
Giulia Rigotto, Lorena Zentilin, Tullio Pozzan, Emy Basso
Summary: The study on the role of mitochondria and Ca2+ signaling in a Familial Alzheimer's disease model revealed early alterations in mitochondria physiology under stress conditions, such as reduced maximal respiration, decreased ability to sustain membrane potential, and a slower return to basal matrix Ca2+ levels after mild excitotoxic stimulus. Treatment with an inhibitor of the permeability transition pore attenuated some of these mitochondrial dysfunctions, showing promise in ameliorating mitochondrial and cellular functioning in AD to prevent or slow down cell loss in the disease.
Article
Neurosciences
Dinesh C. Joshi, Chuan-Li Zhang, Deepali Mathur, Alex Li, Gaurav Kaushik, Zu-Hang Sheng, Shing-Yan Chiu
Summary: The interaction between pro-inflammatory cytokine IL-1/I and NMDA triggers the misplacement of mitochondrial anchor protein SNPH into neuronal dendrites, leading to excitotoxicity. Blocking the interaction between IL-1/I and NMDAR can prevent the intrusion of SNPH into dendrites. Neuronal toxicity caused by IL-1/I or NMDA is significantly reduced in SNPH-/- neurons. Targeting dendritic SNPH in the tripartite IL-1/I/NMDAR/SNPH interaction could be a strategic approach to ameliorate neurotoxicity in inflammatory diseases.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Ophthalmology
Hong-li Liu, Fang-Yuan Hu, Ping Xu, Ji-Hong Wu
Summary: This study found that metformin improves the structure and function of retinal neurons by regulating mitophagy. In vitro and in vivo experiments showed that metformin significantly increased cell viability and reduced apoptosis. In an animal model, metformin treatment significantly increased the number of surviving retinal ganglion cells and improved retinal function. Furthermore, metformin protected mitochondria by regulating the expression of mitophagy-related genes and proteins.
EXPERIMENTAL EYE RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Wen Zhang, Fanghua Ye, Nan Pang, Miriam Kessi, Juan Xiong, Shimeng Chen, Jing Peng, Li Yang, Fei Yin
Summary: This study elucidates the role and mechanism of SERCA2b gene mutants in glutamate-induced excitotoxicity, showing that they worsen cell damage by accelerating Ca2+ depletion and causing ER stress and mitochondrial Ca2+ overload. Enhancing SERCA2b pumping capacity or inhibiting Ca2+ leakage can alleviate this toxicity response.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Uri Nimrod Ramirez-Jarquin, Violeta Gisselle Lopez-Huerta, Ricardo Tapia
Summary: Damage is a central mechanism in neurological disorders, including Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS). This study investigated the ultrastructural mitochondrial alterations in spinal motor neurons during chronic AMPA-induced excitotoxicity, a relevant mechanism in ALS. The findings showed mitochondrial swelling and crest disruption, changes in mitochondrial morphology, and evidence of mitochondrial DNA damage. Understanding these mitochondrial alterations can contribute to the development of treatments for motor neuron degeneration in ALS patients.
Article
Neurosciences
Theresa S. Rimmele, Shaomin Li, Jens Velde Andersen, Emil W. Westi, Alexander Rotenberg, Jianlin Wang, Blanca Irene Aldana, Dennis J. Selkoe, Chiye J. Aoki, Chris G. Dulla, Paul Allen Rosenberg
Summary: The major glutamate transporter GLT-1 is expressed in both presynaptic terminals and astrocytes in the mammalian central nervous system. While astrocytic GLT-1 is believed to primarily regulate glutamate homeostasis, the function of neuronal GLT-1 has remained relatively unexplored. Conditional knockout of GLT-1 in neurons resulted in impaired stimulus-evoked field extracellular postsynaptic potentials (fEPSPs), suggesting a crucial role for neuronal GLT-1 in excitatory synaptic transmission. Excitotoxicity may underlie the transmission failure observed in neuronal GLT-1 knockout mice, with potential metabolic perturbations contributing to vulnerability to NMDA receptor activation.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Jens Andersen, Arne Schousboe, Alexei Verkhratsky
Summary: Astrocytes play a significant role in the development of Alzheimer's disease. They collaborate closely with neurons through neurotransmitter recycling, which is essential for neurotransmission. The metabolic changes in astrocytes during Alzheimer's disease can have a profound impact on neurotransmitter recycling and deprive neurons of metabolic support, leading to synaptic dysfunction and neurodegeneration.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Cell Biology
Sophie L. Allen, Alex P. Seabright, Jonathan Quinlan, Amritpal Dhaliwal, Felicity R. Williams, Nicholas H. F. Fine, David J. Hodson, Matthew J. Armstrong, Ahmed M. Elsharkaway, Carolyn A. Greig, Yu-Chiang Lai, Janet M. Lord, Gareth G. Lavery, Leigh Breen
Summary: This study utilized an in vitro model of liver disease to investigate the effects of serum from liver disease patients on myotube diameter, mitochondrial respiration, and muscle-related protein content. The findings suggest potential mechanisms underlying sarcopenia development in liver disease patients.
Review
Plant Sciences
Susmita Sett, Ashish Prasad, Manoj Prasad
Summary: Viruses are acellular pathogens that cause severe infections in plants, resulting in worldwide crop losses every year. Understanding the defense mechanisms of plants against viruses is crucial for devising proper management strategies. Plant resistance genes can regulate defense against viruses by eliciting a hypersensitive response and activating necrotic cell death, thereby stopping the spread of the disease.
TRENDS IN PLANT SCIENCE
(2022)
Article
Multidisciplinary Sciences
Dan Sun, Vasily S. Minkov, Shirin Mozaffari, Ying Sun, Yanming Ma, Stella Chariton, Vitali B. Prakapenka, Mikhail Eremets, Luis Balicas, Fedor F. Balakirev
Summary: The superconductivity of LaH10 is found to be influenced by pressure and magnetic field, with lattice vibrations strongly affecting the superconducting coupling. This has important implications for understanding the superconductivity of metallic hydrogen.
NATURE COMMUNICATIONS
(2021)
Review
Pharmacology & Pharmacy
Josephine H. Li, Jose C. Florez
Summary: The global epidemic of type 2 diabetes presents a significant challenge to public health and is a major cause of disease and death. Current therapies for type 2 diabetes only address symptoms such as hyperglycemia, without directly addressing the underlying disease process. This article highlights the contributions of genomic discovery to understanding the heterogeneity of type 2 diabetes, reviews relevant pharmacogenetic discoveries in commonly prescribed glucose-lowering agents, discusses how pharmacogenetics can advance precision medicine, and identifies important research gaps for guiding treatment choices.
Review
Cell Biology
Gabriel Nascimento-dos-Santos, Eduardo De-Souza-Ferreira, Rafael Linden, Antonio Galina, Hilda Petrs-Silva
Summary: Mitochondria are essential for aerobic respiration and the production of ATP in eukaryotic cells. Disruption of mitochondrial homeostasis is associated with various pathological conditions, and transplanting metabolically active mitochondria has shown therapeutic potential in disease models. Research on mitotherapy as a promising approach for treatment is advancing with promising outcomes.
Review
Environmental Sciences
Samuli Korpinen, Maria Kahlert, Harri Kuosa, Leoni Mack, Kristian Meissner, Heikki Pitkanen, Timo Pyhalahti, Laura Uusitalo
Summary: Efforts to renew marine ecosystem monitoring in accordance with the environmental legislation of the European Union (EU) have been slow, despite the benefits of new methods. This study reviews the adoption of new methods in EU member states implementing the EU marine strategy framework directive (MSFD) and assesses their level of adoption. The results show varying levels of adoption and suggest that the methods used in European and regional programs may influence national adoption.
FRONTIERS IN MARINE SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Michela Rossini, Paola Pizzo, Riccardo Filadi
Summary: The strategic importance of inter-organelle cross-talk in regulating physiological cellular mechanisms is well established. Efforts have been made to study these organelle interactions and understand their functional roles within the cell. The available methods for investigating membrane contact sites have both advantages and disadvantages.
Article
Cell Biology
Riccardo Filadi, Elisa Greotti
Summary: Mitochondria play crucial roles in cellular activities by orchestrating diverse cell signaling pathways, with Ca2+ being one of the most significant targets. Understanding the role of mitochondrial Ca2+ signaling in physiological and pathological processes can provide insights into cellular functions and disease mechanisms. Specifically, investigating mitochondrial Ca2+ alterations in various pathological conditions, such as Alzheimer's disease, highlights the pivotal role of mitochondria in pathology.
Article
Biology
Luana Naia, Catarina M. Pinho, Giacomo Dentoni, Jianping Liu, Nuno Santos Leal, Duarte M. S. Ferreira, Bernadette Schreiner, Riccardo Filadi, Ligia Fao, Niamh M. C. Connolly, Pontus Forsell, Gunnar Nordvall, Makoto Shimozawa, Elisa Greotti, Emy Basso, Pierre Theurey, Anna Gioran, Alvin Joselin, Marie Arsenian-Henriksson, Per Nilsson, A. Cristina Rego, Jorge L. Ruas, David Park, Daniele Bano, Paola Pizzo, Jochen H. M. Prehn, Maria Ankarcrona
Summary: This study established a large-scale screening platform for mitochondrial-based modulators and identified luteolin as a compound with potential therapeutic validity for various human diseases by increasing mitochondrial activity through enhancing interactions between mitochondria and endoplasmic reticulum. The findings suggest a novel mechanism for luteolin's modulation of mitochondrial function in neuronal models and potential therapeutic applications.
Review
Cell Biology
Celine Deneubourg, Mauricio Ramm, Luke J. Smith, Olga Baron, Kritarth Singh, Susan C. Byrne, Michael R. Duchen, Mathias Gautel, Eeva-Liisa Eskelinen, Manolis Fanto, Heinz Jungbluth
Summary: Primary dysfunction of autophagy due to Mendelian defects affecting core components of the autophagy machinery or closely related proteins has been recognized as an important cause of genetic disease. These disorders can present throughout life, with severe early-onset neurodevelopmental disorders and more common adult-onset neurodegenerative disorders. The overlap between congenital autophagy disorders and other multisystem diseases reflects the complex roles of proteins and suggests a promising area for future research.
Article
Biochemistry & Molecular Biology
Jose Saura-Esteller, Ismael Sanchez-Vera, Sonia Nunez-Vazquez, Ana M. Cosialls, Pau Gama-Perez, Gauri Bhosale, Lorena Mendive-Tapia, Rodolfo Lavilla, Gabriel Pons, Pablo M. Garcia-Roves, Michael R. Duchen, Daniel Iglesias-Serret, Joan Gil
Summary: Fluorizoline induces ER stress and activation of the integrated stress response in HEK293T and U2OS cells, protecting against fluorizoline-induced apoptosis through eIF2α phosphorylation and increased protein levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Luisa Galla, Nicola Vajente, Diana Pendin, Paola Pizzo, Tullio Pozzan, Elisa Greotti
Summary: Calcium (Ca2+) plays a crucial role in controlling both physiological and pathological cellular processes, with a new nuclear-targeted calcium probe developed for more accurate quantitative measurements. This study successfully demonstrated similar levels of calcium in cytoplasm and nucleoplasm in resting and stimulated cells, highlighting the importance of localized calcium monitoring for cell function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Nelly Redolfi, Paloma Garcia-Casas, Chiara Fornetto, Sonia Sonda, Paola Pizzo, Diana Pendin
Summary: Calcium signaling is crucial for brain physiology, playing a role in processes like synaptic transmission and neuronal survival. Homeostasis of Ca2+ is disrupted in aging and neurodegenerative diseases, highlighting the importance of understanding these processes for neuroscience. Ca2+ imaging in animal models shows potential for exploring the pathogenesis of neurodegenerative diseases by studying brain function.
Review
Cell Biology
Chih-Yao Chung, Gabriel E. Valdebenito, Anitta R. Chacko, Michael R. Duchen
Summary: Mutations in mitochondrial DNA have a significant impact on cellular energy homeostasis and signaling pathways, influencing disease presentation and progression.
TRENDS IN CELL BIOLOGY
(2022)
Article
Biology
Andres De la Rossa, Marine H. Laporte, Simone Astori, Thomas Marissal, Sylvie Montessuit, Preethi Sheshadri, Eva Ramos-Fernandez, Pablo Mendez, Abbas Khani, Charles Quairiaux, Eric B. Taylor, Jared Rutter, Jose Manuel Nunes, Alan Carleton, Michael R. Duchen, Carmen Sandi, Jean-Claude Martinou
Summary: Neuronal excitation relies on ATP from oxidative phosphorylation, and deficient oxidative phosphorylation can lead to hyperexcitability in neurons. Inhibiting GABA activity in mice with deficient mitochondrial pyruvate carrier (MPC) led to seizures and death, but providing ketone bodies restored energy and attenuated seizures. These findings provide insights into epilepsy and other neuropathologies associated with energy deficits.
Article
Biology
Liliana M. Almeida, Brigida R. Pinho, Michael R. Duchen, Jorge M. A. Oliveira
Summary: PERK plays a crucial role in responding to stress in the endoplasmic reticulum and mitochondria, regulating mitochondrial dynamics, metabolism, and quality control by activating multiple protective pathways. Pharmacological activation of PERK shows protective effects in neurodegenerative and metabolic diseases, while PERK inhibition exhibits protective effects in other disease models.
BIOLOGICAL REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Filippo Fornasiero, Cristina Scapin, Maurizio Vitadello, Paola Pizzo, Luisa Gorza
Summary: This study reveals the role of Grp94/gp96 in cytoprotection by regulating SERCA2 and improving Ca2+ homeostasis. It demonstrates that Grp94 can co-immunoprecipitate with non-client proteins and form a multiprotein complex involving active nNOS, contributing to antioxidant cytoprotection. Moreover, in breast cancer cells, the presence of Grp94-nNOS, SERCA2, and PMCA co-immunoprecipitation is associated with increased oxidant-induced apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Cell Biology
Riccardo Filadi, Paola Pizzo
Article
Cell Biology
Lucia Barazzuol, Domenico Cieri, Nicola Facchinello, Tito Cali, Philip Washbourne, Francesco Argenton, Paola Pizzo
Summary: This study generated a zebrafish line with a psen2 knockout, and found that the absence of the protein does not significantly affect Notch signaling, but leads to an exaggeration of locomotor response, a decrease in ER-mitochondria contacts, and an increase in basal autophagy. The protein also plays a role in mitochondrial axonal transport, and its downregulation reduces organelle flux in zebrafish sensory neurons. These findings highlight zebrafish as a valuable model organism for studying PS2 functions and testing potential therapies for Alzheimer's disease.
Editorial Material
Biochemistry & Molecular Biology
Gabriel E. Valdebenito, Anitta R. Chacko, Michael R. Duchen
Summary: The mitochondrial F1Fo-ATP synthase can both synthesize ATP and pump protons, with potential implications for diseases. In a recent study, Acin-Perez et al. identified (+)-epicatechin as a compound that selectively inhibits ATP hydrolysis without affecting ATP synthesis. They found that this compound has significant benefits for cell and tissue function in disease models, suggesting a novel therapeutic approach for mitochondrial disease.
