Article
Endocrinology & Metabolism
Wan-Ting Dong, Li-Hong Long, Qiao Deng, Duo Liu, Jia-Lin Wang, Fang Wang, Jian-Guo Chen
Summary: This study reveals the crucial role of Drp1-dependent mitochondrial fission in neuronal energy metabolism and synaptic efficacy under chronic stress. Inhibiting or reducing Drp1 can improve depressive-like behavior, while promoting Drp1 fission increases stress susceptibility, which can be alleviated by coenzyme Q10.
Article
Biochemistry & Molecular Biology
Dezhen Tu, Ravikanth Velagapudi, Yun Gao, Jau-Shyong Hong, Hui Zhou, Hui-Ming Gao
Summary: This study investigates the expression patterns, regulatory mechanisms, and pathological roles of neuronal NADPH oxidase in inflammation-associated neurodegeneration. The results show that NOX2 is persistently upregulated in neurons during chronic neuroinflammation and is associated with oxidative stress and neurodegeneration. Inhibition of neuronal NOX2 can block the degenerative effects of inflammatory mediators and prevent neurodegeneration.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Gastroenterology & Hepatology
Tuo Hu, Surendra K. Shukla, Enza Vernucci, Chunbo He, Dezhen Wang, Ryan J. King, Kanupriya Jha, Kasturi Siddhanta, Nicholas J. Mullen, Kuldeep S. Attri, Divya Murthy, Nina Chaika, Ravi Thakur, Scott E. Mulder, Camila G. Pacheco, Xiao Fu, Robin R. High, Fang Yu, Audrey Lazenby, Clemens Steegborn, Ping Lan, Kamiya Mehla, Dante Rotili, Sarika Chaudhary, Sergio Valente, Marco Tafani, Antonello Mai, Johan Auwerx, Eric Verdin, David Tuveson, Pankaj K. Singh
Summary: SIRT5 functions as a key tumor suppressor in PDAC, inhibiting tumor cell proliferation and correlating with a favorable prognosis. Loss of SIRT5 promotes PDAC development and malignant transformation.
Article
Cell Biology
Doris Chen, Wanjia Yu, Laura Aitken, Frank Gunn-Moore
Summary: This study identifies Willin/FRMD6 as a potential risk gene for Alzheimer's disease (AD), and demonstrates the direct effects of A beta on its expression. The study also reveals mitochondrial oxidative stress as a novel mechanism underlying the role of Willin/FRMD6 in AD pathogenesis. Additionally, the study shows that knockdown of Willin/FRMD6 leads to mitochondrial dysfunction and upregulation of ERK1/2 signaling, which are key early features of AD. Increasing Willin/FRMD6 expression may serve as a therapeutic strategy for protecting against A beta-induced mitochondrial and neuronal dysfunction.
Article
Environmental Sciences
En-Ming Chang, Chia-Chia Chao, Mei-Ting Wang, Chia-Lang Hsu, Po-Chun Chen
Summary: PM2.5 exposure causes mitochondrial fragmentation and induces pulmonary fibrosis in type II alveolar cells, leading to collagen accumulation in lung tissue.
ENVIRONMENTAL TOXICOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Pasquale Picone, Gaetana Porcelli, Celeste Caruso Bavisotto, Domenico Nuzzo, Giacoma Galizzi, Pier Luigi San Biagio, Donatella Bulone, Marta Di Carlo
Summary: Synaptosomes have been demonstrated to be a natural vehicle for the delivery of molecules and organelles to neuronal cells, showing potential in replacing damaged mitochondria with healthy ones for treating neuronal mitochondrial dysfunction-related diseases.
JOURNAL OF NANOBIOTECHNOLOGY
(2021)
Article
Biology
Maria Mercado-Gomez, Endika Prieto-Fernandez, Naroa Goikoetxea-Usandizaga, Laura Vila-Vecilla, Mikel Azkargorta, Miren Bravo, Marina Serrano-Macia, Leire Egia-Mendikute, Ruben Rodriguez-Agudo, Sofia Lachiondo-Ortega, So Young Lee, Alvaro Eguileor Gine, Claudia Gil-Pitarch, Irene Gonzalez-Recio, Jorge Simon, Petar Petrov, Ramiro Jover, Luis Alfonso Martinez-Cruz, June Ereno-Orbea, Teresa Cardoso Delgado, Felix Elortza, Jesus Jimenez-Barbero, Ruben Nogueiras, Vincent Prevot, Asis Palazon, Maria L. Martinez-Chantar
Summary: SARS-CoV-2 pseudovirus infects human hepatocytes and causes metabolic reprogramming and impaired mitochondrial activity. Patients with fatty liver are more susceptible to infection, but the use of metformin can reduce the risk of infection.
COMMUNICATIONS BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Chakravarthy Garlapati, Shriya Joshi, Ravi Chakra Turaga, Manjari Mishra, Michelle D. Reid, Shobhna Kapoor, Liana Artinian, Vincent Rehder, Ritu Aneja
Summary: Etn alters GLUT1 trafficking leading to metabolic stress in PCa, upregulates phosphatidylethanolamine (PE) to modulate membrane fluidity and affect mitochondrial structure and function, induces autophagy in PCa cells, thereby promoting apoptosis.
Review
Cell Biology
Grant C. C. Walters, Yuriy M. M. Usachev
Summary: Mitochondria play essential roles in cellular function, including ATP synthesis, reactive oxygen species production, calcium buffering, and apoptotic signaling. In neurons, calcium buffering is particularly important for regulating various calcium-dependent functions. Recent discoveries of molecular components involved in mitochondrial calcium transport have shed light on the roles of mitochondrial calcium regulation in neuronal function and its implications in neurological diseases. This review discusses the multiple roles of mitochondrial calcium uptake and release mechanisms in normal neuronal function and provides insight into the calcium-dependent mechanisms underlying mitochondrial dysfunction in neurological diseases. The targeting of calcium uptake and release mechanisms could potentially lead to novel therapeutic strategies for these diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Scott A. Tiscione, Maria Casas, Jonathan D. Horvath, Vincent Lam, Keiko Hino, Daniel S. Ory, L. Fernando Santana, Sergi Simo, Rose E. Dixon, Eamonn J. Dickson
Summary: The study shows that loss-of-function, knockout, or neurodegenerative disease-causing mutations in NPC1 can lead to damaging alterations in the expression and distribution of IP3R1, causing cell death. This process is mediated by SREBP-dependent increases in PS1, with mutants of PS1 recapitulating the Ca2+ phenotypes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Kerry C. Ryan, Jocelyn T. Laboy, Kenneth R. Norman
Summary: Mitochondrial dysfunction and oxidative stress are major contributors to neurodegenerative diseases. This study reveals that elevated mitochondrial calcium levels, rather than cytosolic calcium levels, lead to increased reactive oxygen species (ROS) production and subsequent neurodegeneration in sel-12 mutants. The study also identifies mTORC1 signaling as a critical factor in sustaining high ROS levels in sel-12 mutants.
Review
Biochemistry & Molecular Biology
Lauren Elizabeth Millichap, Elisabetta Damiani, Luca Tiano, Iain P. Hargreaves
Summary: Mitochondrial dysfunction and oxidative stress play critical roles in the pathophysiology of neurodegenerative diseases, leading to neuronal damage. The brain is highly vulnerable to oxidative damage due to its high metabolic demand and low antioxidant defense systems, which can result in tissue damage and activation of inflammatory processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Kyeoung-Hwa Kim, Kyung-Ah Lee
Summary: This study identified the effects of human placenta-derived mesenchymal stem cell therapy on aging, including weight loss, increased insulin-like growth factor-I levels, altered metabolites and protein levels, and the therapeutic targeting of serotonin for reversing aging-associated liver degeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Susanna Campesan, Ivana del Popolo, Kyriaki Marcou, Anna Straatman-Iwanowska, Mariaelena Repici, Kalina Boytcheva, Victoria E. Cotton, Natalie Allcock, Ezio Rosato, Charalambos P. Kyriacou, Flaviano Giorgini
Summary: This study shows that Huntington's disease is a fatal neurodegenerative disease with limited treatment options. The researchers used high-resolution respirometry to reveal defective mitochondrial function in a fruit fly model of the disease and found that enhancing mitochondrial function can improve these defects. Furthermore, they discovered that co-expression of the protein parkin significantly enhances mitochondrial respiration and rescues neurodegeneration, viability, and longevity in the fruit flies.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Biology
Hope I. Needs, Margherita Protasoni, Jeremy M. Henley, Julien Prudent, Ian Collinson, Goncalo C. Pereira
Summary: Mitochondrial protein import is crucial for normal organelle physiology, and impaired import can lead to defective mitochondrial respiration and various diseases. Activation of stress response pathways is necessary to overcome dysfunction and restore proteostasis in mitochondria and cells.
Article
Cell Biology
Audrey M. Thiebaut, Izaskun Buendia, Vanessa Ginet, Eloise Lemarchand, Mehdi Boutagouga Boudjadja, Yannick Hommet, Laurent Lebouvier, Charlotte Lechevallier, Mike Maillasson, Elodie Hedou, Nicole Deglon, Franck Oury, Marina Rubio, Joan Montaner, Julien Puyal, Denis Vivien, Benoit D. Roussel
Summary: Cerebral ischemia induces harmful autophagy in neurons, while PLAT/tPA can mediate neuroprotection by decreasing autophagy levels. The research discovered that PLAT/tPA degrades IGFBP3 to increase the bioavailability of IGF1, leading to the activation of neuroprotective pathways.
Article
Biotechnology & Applied Microbiology
Elodie Leroux, Romain Perbet, Raphaelle Caillierez, Kevin Richetin, Sarah Lieger, Jeanne Espourteille, Thomas Bouillet, Severine Begard, Clement Danis, Anne Loyens, Nicolas Toni, Nicole Deglon, Vincent Deramecourt, Susanna Schraen-Maschke, Luc Buee, Morvane Colin
Summary: Tauopathies are neurodegenerative diseases characterized by tau inclusions in brain cells. This study suggests that extracellular vesicles (EVs) may play a role in the prion-like propagation of tau pathology among different tauopathies. The researchers isolated EVs from different brain regions in various tauopathies and found that EVs from Alzheimer's disease patients contained pathological tau species that could induce tau lesions in vivo. These findings have implications for diagnostic and therapeutic strategies.
Article
Biochemistry & Molecular Biology
Mara Mennuni, Roberta Filograna, Andrea Felser, Nina A. Bonekamp, Patrick Giavalisco, Oleksandr Lytovchenko, Nils-Goran Larsson
Summary: Resistance to mitochondrial transcription inhibitors (IMTs) is mainly achieved through compensatory increase in mitochondrial DNA expression and cellular metabolites. Loss of genes related to von Hippel-Lindau and mTORC1 pathways confers resistance to the inhibitors. Downregulation of mitochondrial transcription factor A and inhibition of mitochondrial translation also impairs survival of resistant cells.
Article
Cell Biology
Gulzar A. Wani, Hans-Georg Sprenger, Kristiano Ndoci, Srikanth Chandragiri, Richard James Acton, Desiree Schatton, Sandra M. V. Kochan, Vignesh Sakthivelu, Milica Jevtic, Jens M. Seeger, Stefan Mueller, Patrick Giavalisco, Elena I. Rugarli, Elisa Motori, Thomas Langer, Matteo Bergami
Summary: This study reveals the importance of YME1L peptidase in regulating the self-renewal of neural stem and progenitor cells (NSPCs). YME1L controls the rewiring of the mitochondrial proteome, ensuring the metabolic plasticity of NSPCs and preventing premature differentiation.
Article
Biochemistry & Molecular Biology
Xuefeng Zhu, Xie Xie, Hrishikesh Das, Benedict G. Tan, Yonghong Shi, Ali Al-Behadili, Bradley Peter, Elisa Motori, Sebastian Valenzuela, Viktor Posse, Claes M. Gustafsson, B. Martin Haellberg, Maria Falkenberg
Summary: The non-coding RNA molecule 7S RNA regulates mitochondrial transcription in mammalian cells by inducing POLRMT dimerization, which prevents transcription initiation.
Article
Endocrinology & Metabolism
Marc Briquet, Anne-Berengere Rocher, Maxime Alessandri, Nadia Rosenberg, Haissa de Castro Abrantes, Joel Wellbourne-Wood, Celine Schmuziger, Vanessa Ginet, Julien Puyal, Etienne Pralong, Roy Thomas Daniel, Stefan Offermanns, Jean-Yves Chatton
Summary: Lactate can be utilized by neurons as an energy source and can decrease synaptic activity through activation of HCAR1 receptor, making HCAR1 an attractive target for the treatment of epilepsy.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Genetics & Heredity
Dusanka Milenkovic, Adrian Sanz-Moreno, Julia Calzada-Wack, Birgit Rathkolb, Oana Veronica Amarie, Raffaele Gerlini, Antonio Aguilar-Pimentel, Jelena Misic, Marie-Lune S. Simard, Eckhard T. Wolf, Helmut S. Fuchs, Valerie T. Gailus-Durner, Martin Hrabe S. de Angelis, Nils-Goeran T. Larsson
Summary: The authors addressed the controversy surrounding the role of the mitochondrial genome and MGME1 in mtDNA metabolism by studying knockout mice. They found that loss of MGME1 leads to the formation of linear deleted mtDNA fragments, contradicting previous reports. In addition, aged knockout mice developed various age-associated pathologies, including weight loss, cataract, retinopathy, kidney inflammation, glomerular changes, fibrosis, and nephrotic syndrome. These findings suggest that defective mtDNA replication can trigger an immune response and cause progressive pathology in aging kidneys.
Article
Neurosciences
Nadia Rosenberg, Maria Reva, Francesca Binda, Leonardo Restivo, Pauline Depierre, Julien Puyal, Marc Briquet, Yann Bernardinelli, Anne-Berengere Rocher, Henry Markram, Jean-Yves Chatton
Summary: Recent research suggests that targeting astrocytes and their mitochondria could be an effective strategy to prevent early-stage Alzheimer's disease, as it can prevent metabolic abnormalities, hippocampal atrophy, and cognitive decline.
Article
Biochemistry & Molecular Biology
Cristina Remes, Anas Khawaja, Sarah F. Pearce, Adam M. Dinan, Shreekara Gopalakrishna, Miriam Cipullo, Vasileios Kyriakidis, Jingdian Zhang, Xaquin Castro Dopico, Olessya Yukhnovets, Ilian Atanassov, Andrew E. Firth, Barry Cooperman, Joanna Rorbach
Summary: The detailed mechanism of mitochondrial translation in human mitochondria remains unclear. This study reveals that leaderless mRNA transcripts can be directly loaded onto assembled 55S mitochondrial ribosomes in human mitochondria, but not onto the small subunit, and this process requires initiator fMet-tRNA(Met) binding. Furthermore, this study demonstrates that mtIF3 is not involved in translation of leaderless mitochondrial transcripts but is essential for translation of ATP6 in the bicistronic ATP8/ATP6 transcript. These findings provide insights into the evolutionary divergence of mitochondrial translation and enhance our understanding of a critical process in eukaryotic metabolism.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Annika Kruger, Cristina Remes, Dmitrii Igorevich Shiriaev, Yong Liu, Henrik Spahr, Rolf Wibom, Ilian Atanassov, Minh Duc Nguyen, Barry S. Cooperman, Joanna Rorbach
Summary: This article investigates the noncanonical stop codons AGA and AGG in the mammalian mitochondrial genome. The authors demonstrate that mtRF1 protein triggers translation termination at AGA and AGG, placing mtRF1 among mitochondrial translation factors. The study reveals the role of mtRF1 in translation termination at non-canonical stop codons in mitochondria.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Laura S. Kremer, Lyuba V. Bozhilova, Diana Rubalcava-Gracia, Roberta Filograna, Mamta Upadhyay, Camilla Koolmeister, Patrick F. Chinnery, Nils-Goran Larsson
Summary: In this study, the role of autophagy in germline purifying selection of mtDNA was investigated by mating different autophagy-deficient mouse models with mice carrying a pathogenic tRNA(Ala) gene mutation. The results showed that Bcl2l13 had a significant effect on the selection process, while Ulk1 and Ulk2 had weaker effects, and Parkin had no statistically significant impact. This study provides experimental evidence for the distinct roles of autophagy in germline purifying selection of mtDNA and establishes a framework for future studies on this process.
Article
Cell Biology
Romain Perbet, Valentin Zufferey, Elodie Leroux, Enea Parietti, Jeanne Espourteille, Lucas Culebras, Sylvain Perriot, Renaud Du Pasquier, Severine Begard, Vincent Deramecourt, Nicole Deglon, Nicolas Toni, Luc Buee, Morvane Colin, Kevin Richetin
Summary: Tau protein accumulation in astrocytes is involved in neurodegenerative disorders. The origins of 3R and 4R isoforms of tau in astrocytes remain unclear. This study demonstrates that neurons with accumulated 3R or 4R tau have the ability to transfer tau to astrocytes through extracellular vesicles (EVs). Tau-containing EVs disrupt the mitochondrial system of astrocytes and the damage is more severe with 3R tau-containing EVs. EVs from the brain fluid of tauopathy patients also affect mitochondrial function in astrocytes derived from human induced pluripotent stem cells (iPSCs).
Article
Biology
Jun Yong Kim, Ilian Atanassov, Frederik Dethloff, Lara Kroczek, Thomas Langer
Summary: Mitochondrial remodeling and metabolic rewiring occur during cellular senescence, with an overall increase in mitochondrial activities. Proteomic analyses revealed extensive reprogramming of the mitochondrial proteome, and identified metabolic pathways that are rewired in different kinetics upon establishment of senescence. Metabolic flux analyses confirmed these signatures, highlighting metabolic rewiring as a central feature of mitochondria in cellular senescence.
LIFE SCIENCE ALLIANCE
(2023)
Article
Biology
Fynn M. Hansen, Laura S. Kremer, Ozge Karayel, Isabell Bludau, Nils-Goeran Larsson, Inge Kuehl, Matthias Mann
Summary: Mitochondria are essential organelles with tissue-specific functions, and phosphorylation plays an important role in regulating these functions. This study used mass spectrometry to quantitatively analyze the protein and phosphoprotein profiles of mitochondria from different tissues. The results provide a comprehensive map of mitochondrial proteins and phosphorylation events, and reveal tissue-specific regulation at the phosphoproteome level. The study reproduces known phosphorylation events and identifies new phosphorylation clusters associated with mitochondrial fusion.
LIFE SCIENCE ALLIANCE
(2023)
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.