Article
Biochemistry & Molecular Biology
Juliane C. Campos, Ziyun Wu, Paige D. Rudich, Sonja K. Soo, Meeta Mistry, Julio C. b Ferreira, T. Keith Blackwell, Jeremy M. Van Raamsdonk
Summary: Disrupting subunits of the mitochondrial electron transport chain results in the upregulation of genes involved in innate immunity, which promotes increased resistance to bacterial pathogens and extended longevity in long-lived mitochondrial mutants. Both the p38-mediated innate immune signaling pathway and the mitoUPR act together on the same innate immunity genes to modulate lifespan.
Article
Biology
James P. Held, Gaomin Feng, Benjamin R. Saunders, Claudia Pereria, Kristopher Burkewitz, Maulik R. Patel, Xiaochen Wang
Summary: Researchers have discovered a new RNA-based cellular pathway, mediated by the enzyme HOE-1, that activates the mitochondrial unfolded protein response (UPRmt) by regulating the transcription factors ATFS-1 and DVE-1. This pathway does not rely on the integrated stress response and is likely mediated by tRNAs. The subcellular localization of HOE-1 is responsive to mitochondrial stress and is negatively regulated by ATFS-1.
Article
Pharmacology & Pharmacy
Moonjung Hyun, Laxmi Rathor, Hye-Jin Kim, Taylor McElroy, Kwang Hyun Hwang, Stephanie Wohlgemuth, Shayla Curry, Rui Xiao, Christiaan Leeuwenburgh, Jeong-Doo Heo, Sung Min Han
Summary: The study compared the effects of BPA and its substitutes on nematodes and mammalian cells and found that these BPA alternatives also have detrimental effects on development, growth, reproduction, lifespan, and mitochondrial function.
Review
Cell Biology
Zixin Zhou, Yumei Fan, Ruikai Zong, Ke Tan
Summary: Mitochondria are involved in various cellular functions and are regulated by the mitochondrial unfolded protein response (UPRmt) in response to environmental stresses. The regulatory mechanisms and factors involved in UPRmt differ between Caenorhabditis elegans and mammals. Exploring UPRmt can provide new directions and strategies for the treatment of human diseases.
AGEING RESEARCH REVIEWS
(2022)
Article
Medicine, Research & Experimental
Wenshu Cong, Yajie Wang, Chunhui Yuan, Mei Xu, Han Wang, You Hu, Xuyan Dai, Yuhua Weng, Peter Timashev, Xing-Jie Liang, Yuanyu Huang
Summary: Mitochondrial unfolded protein response (UPRmt) is a pathway that regulates metabolism and lifespan. The use of dimercapto succinic acid (DMSA)-modified cobalt oxide nanoparticles (Co3O4 NPs) as an UPRmt activator in C. elegans shows potential in extending healthy lifespan by fine-tuning mitochondrial dynamics and inducing an imbalance between mtDNA and nDNA.
Article
Biochemistry & Molecular Biology
Namasthee Harris-Gauthier, Annika Traa, Abdelrahman AlOkda, Alibek Moldakozhayev, Ulrich Anglas, Sonja K. Soo, Jeremy M. Van Raamsdonk
Summary: Mild impairment of mitochondrial function can increase lifespan in genetic model organisms. The upregulation of genes involved in the mitochondrial thioredoxin system, mediated by the mitochondrial unfolded protein response, is specifically required for the longevity of mitochondrial mutants. The mitochondrial thioredoxin system also plays a role in stress resistance.
Article
Cell Biology
Jing Tian, Caroline Geiss, Kim Zarse, Corina T. Madreiter-Sokolowski, Michael Ristow
Summary: Green tea catechins such as EGCG and ECG have been found to extend healthspan and lifespan in Caenorhabditis elegans by inhibiting mitochondrial complex I and temporarily lowering ATP levels, leading to activation of SKN-1 and DAF-16. These catechins also reduce fat content, enhance ROS defense, and ultimately improve overall healthspan through adaptive responses.
Article
Cell Biology
Eirini Taouktsi, Eleni Kyriakou, Stefanos Smyrniotis, Fivos Borbolis, Labrina Bondi, Socratis Avgeris, Efstathios Trigazis, Stamatis Rigas, Gerassimos E. Voutsinas, Popi Syntichaki
Summary: Disruption of LonP1 leads to mitochondrial dysfunction and diverse cellular and organismal stress responses in both worms and cancer cells.
Review
Biochemistry & Molecular Biology
Hagai Rottenberg
Summary: It is widely reported that the mitochondrial membrane potential, increment ψm, is reduced in aging animals. It was recently suggested that the lower increment ψm in aged animals modulates mitochondrial bioenergetics and that this effect is a major cause of aging since artificially increased increment ψm in C. elegans increased lifespan. The activation of the voltage-gated mitochondrial permeability transition pore (mPTP) is the main cause of the increase in depolarized mitochondria in aged cells, inhibiting oxidative phosphorylation, releasing calcium and mROS, and depleting NAD(+), thereby accelerating degenerative diseases and aging. The reported lifespan extension by artificially generated increment ψm in C. elegans is best explained by inhibition of the voltage-gated mPTP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Juan M. Suarez-Rivero, Carmen J. Pastor-Maldonado, Suleva Povea-Cabello, Monica Alvarez-Cordoba, Irene Villalon-Garcia, Marta Talaveron-Rey, Alejandra Suarez-Carrillo, Manuel Munuera-Cabeza, Diana Reche-Lopez, Paula Cilleros-Holgado, Rocio Pinero-Perez, Jose A. Sanchez-Alcazar
Summary: Mitochondrial dysfunction is a common feature in many diseases, and new therapeutic approaches such as activating UPRmt are being explored. UPRmt activation has shown potential benefits in neurodegenerative diseases, cardiopathies, and mitochondrial diseases, but overactivation could lead to undesired side effects.
Review
Neurosciences
Lei Wang, Laura Bianchi
Summary: Mounting evidence supports the key role of glia in organismal ageing, with neuropeptides released by glia acting long distance to regulate ageing and activate the unfolded protein response (UPR) in C. elegans. This cell-nonautonomous activation of UPR leads to extension of lifespan, suggesting potential for novel anti-ageing therapies.
EXPERIMENTAL NEUROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Fabian Schmitt, Gunter P. Eckert
Summary: The study of aging is an important topic, and choosing the right model is crucial. The nematode C. elegans is a well-established model in aging research and has significant advantages in studying bioenergetics and secondary plant metabolites.
Article
Chemistry, Multidisciplinary
Nadia Vertti-Quintero, Simon Berger, Xavier Casadevall i Solvas, Cyril Statzer, Jillian Annis, Peter Ruppen, Stavros Stavrakis, Collin Y. Ewald, Rudiyanto Gunawan, Andrew J. DeMello
Summary: The study demonstrates that protein homeostasis maintenance is a major factor influencing the heterogeneity in HSR dynamics, with individuals with enhanced protein homeostasis fidelity living longer in early adulthood. Age-related decline in protein homeostasis shows a stochastic-onset in day-1 and day-2 adult C. elegans, increasing the heterogeneity in HSR capacity. Additionally, C. elegans embryos exhibit higher HSR and proteostasis capacity compared to young adults, showing a transgenerational contribution to HSR heterogeneity dependent on maternal age.
Article
Cell Biology
Konstantinos Palikaras, Kavya Achanta, Seoyun Choi, Mansour Akbari, Vilhelm A. Bohr
Summary: Evidence suggests that mitochondrial dysfunction precedes tau aggregation in tauopathies, impacting neuronal homeostasis and mobility in animals. Understanding the early molecular mechanisms of mitochondrial dysfunction in tauopathy holds significant clinical and therapeutic value.
Article
Cell Biology
Carmen Martinez-Fernandez, Milana Bergamino, Alfonso Schiavi, David Brena, Natascia Ventura, Sebastian Honnen, Alberto Villanueva, Ernest Nadal, Julian Ceron
Summary: This study used the nematode Caenorhabditis elegans to investigate the effects of cisplatin on mitochondrial functions and neurotoxicity. It was found that a high-glucose diet sensitized the worms to cisplatin and that mitochondrial CED-13 protected cells from cisplatin-induced oxidative stress. In addition, dopamine was shown to have a protective role against cisplatin-induced neurotoxicity.
DISEASE MODELS & MECHANISMS
(2022)
Article
Medicine, Research & Experimental
Aida Abu-Baker, Nawwaf Kharma, Jonathan Perreault, Alanna Grant, Masoud Shekarabi, Claudia Maios, Michele Dona, Christian Neri, Patrick A. Dion, Alex Parker, Luc Varin, Guy A. Rouleau
MOLECULAR THERAPY-NUCLEIC ACIDS
(2019)
Article
Clinical Neurology
Poulomee Bose, Elsa Tremblay, Claudia Maois, Vijay Narasimhan, Gary A. B. Armstrong, Meijiang Liao, J. Alex Parker, Richard Robitaille, Xiao Yan Wen, Christopher Barden, Pierre Drapeau
Review
Cell Biology
Kathrin Schmeisser, J. Alex Parker
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2019)
Article
Cell Biology
James J. Doyle, Celine Vrancx, Claudia Maios, Audrey Labarre, Shunmoogum A. Patten, J. Alex Parker
DISEASE MODELS & MECHANISMS
(2020)
Article
Biochemistry & Molecular Biology
Arnaud Tauffenberger, Pierre J. Magistretti
Summary: Cellular homeostasis is crucial for organism development and aging, with disruption leading to health degradation and death. Reactive oxygen species (ROS) are strongly linked to health decline and neurological disorders, disrupting macromolecules and playing complex roles in cell signaling, particularly in the brain where they impact neuronal survival and synaptic plasticity.
NEUROCHEMICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Priyanka Jamadagni, Maximilian Breuer, Kathrin Schmeisser, Tatiana Cardinal, Betelhem Kassa, J. Alex Parker, Nicolas Pilon, Eric Samarut, Shunmoogum A. Patten
Summary: Mutations in the CHD7 gene cause CHARGE syndrome, characterized by neurological and behavioral problems. Studies in zebrafish and Caenorhabditis elegans models have shown that the small molecule ephedrine can improve GABAergic defects and behavioral anomalies associated with CHD7 deficiency.
Article
Clinical Neurology
Yasmin Fardghassemi, Claudia Maios, J. Alex Parker
Summary: This study conducted a drug screen for SCA3 and identified five small molecule compounds that can restore motor deficiencies, protect against neurodegeneration, and increase the lifespan of worms carrying the ATXN3-CAG89 mutation. Three of these compounds act as modulators for TFEB/HLH-30, a key transcriptional regulator of the autophagy process, and require this gene for their neuroprotective activities.
Article
Multidisciplinary Sciences
James J. Doyle, Claudia Maios, Celine Vrancx, Sarah Duhaime, Babykumari Chitramuthu, Hugh P. J. Bennett, Andrew Bateman, J. Alex Parker
Summary: The article discusses the link between GRN mutations and frontotemporal dementia (FTD) discovered in 2006 and highlights the need for advancing genetic and small-molecule therapeutics for GRN-related FTD. Research using the nematode model, Caenorhabditis elegans, shows that loss of nematode GRN ortholog results in behavioral and molecular defects, and implicates the sphingolipid metabolic pathway in regulating these defects. High-throughput drug screening using nematodes has identified two small molecules with potential therapeutic applications against GRN/pgrn-1 deficiency, offering avenues for mechanistic and therapeutic research into GRN-related neurodegeneration.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Elite Possik, Clemence Schmitt, Anfal Al-Mass, Ying Bai, Laurence Cote, Johanne Morin, Heidi Erb, Abel Oppong, Wahab Kahloan, J. Alex Parker, S. R. Murthy Madiraju, Marc Prentki
Summary: The technique of gastric conduit transposition simplifies the daily practice of esophagectomy. Gastric conduit transposition is a reproducible technique that simplifies esophagectomy in all settings.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Gilles Tossing, Raphael Livernoche, Claudia Maios, Constantin Bretonneau, Audrey Labarre, J. Alex Parker
Summary: Axonal degeneration is observed in various neurodegenerative diseases and may serve as a therapeutic target. This study identified the DLK-1 pathway and the PARP-1 and PARP-2 as consistent modifiers of axonal degeneration in ALS models. Inhibition of PARP-1 and PARP-2 reduces axonal degeneration and improves motor phenotypes.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Jingfang Yu, Merly C. Vogt, Bennett W. Fox, Chester J. J. Wrobel, Diana Fajardo Palomino, Brian J. Curtis, Bingsen Zhang, Henry H. Le, Arnaud Tauffenberger, Oliver Hobert, Frank C. Schroeder
Summary: Untargeted comparative metabolomics revealed the biosynthesis and metabolism pathways of serotonin in nonneuronal tissues, suggesting its important roles in serotonin-dependent phenotypes in C. elegans. Serotonin is abundantly produced in nonneuronal tissues via phenylalanine hydroxylase, in addition to its canonical biosynthesis in neurons via tryptophan hydroxylase. Most serotonin in C. elegans is incorporated into N-acetylserotonin-derived glucosides and further modified via the carboxylesterase CEST-4. Bacterial indole production interacts with serotonin metabolism via CEST-4. These findings indicate the significance of nonneuronal serotonin biosynthesis and metabolism in contributing to serotonin-dependent phenotypes.
NATURE CHEMICAL BIOLOGY
(2023)
Correction
Biochemistry & Molecular Biology
Jingfang Yu, Merly C. Vogt, Bennett W. Fox, Chester J. J. Wrobel, Diana Fajardo Palomino, Brian J. Curtis, Bingsen Zhang, Henry H. Le, Arnaud Tauffenberger, Oliver Hobert, Frank C. Schroeder
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biology
Audrey Labarre, Ericka Guitard, Gilles Tossing, Anik Forest, Eric Bareke, Marjorie Labrecque, Martine Tetreault, Matthieu Ruiz, J. Alex Parker
Summary: This study investigates the neuroprotective effects of the probiotic strain Lacticaseibacillus rhamnosus HA-114 in neurodegenerative disease models and identifies its mechanism of action involving fatty acid metabolism and mitochondrial beta-oxidation. These findings provide a new perspective for interventions to modify the progression of neurodegenerative diseases.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mateusz Wagner, Bingsen Zhang, Arnaud Tauffenberger, Frank C. Schroeder, Aleksandra Skirycz
Summary: The interaction between metabolites and proteins is complex and highly dynamic, playing crucial roles in cellular processes. Advances in omics technologies have enabled global profiling of these interactions, but significant challenges remain, including incomplete chemical characterization of metabolomes.
CURRENT OPINION IN SYSTEMS BIOLOGY
(2021)
Meeting Abstract
Biochemistry & Molecular Biology
H. Sidibe, Y. Khalfallah, G. DiTomasso, A. Aulas, L. Destroimaisons, J. -E. Deshaies, J. Alex Parker, P. Legault, M. Tetreault, C. V. Velde
JOURNAL OF NEUROCHEMISTRY
(2019)