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
Chemistry, Multidisciplinary
Ning Sheng, Zhihui Zhang, Hao Zheng, Congyu Ma, Menglin Li, Zhe Wang, Lulu Wang, Jiandong Jiang, Jinlan Zhang
Summary: This study discovered a molecule called scutellarin (SG) that can treat neurodegenerative diseases by regulating energy metabolism and repairing mitochondrial damage. The molecule was found to protect mitochondria through the PDK-PDC axis and mitochondrial glucose oxidation.
Article
Biochemistry & Molecular Biology
Ines da Silva, Sean Gullette, Cristina Florindo, Neil K. Huang, Thomas Neuberger, A. Catharine Ross, Graca Soveral, Rita Castro
Summary: Ketogenic diets may impact the expression of aquaporins in atherosclerosis models and these aquaporins are related to energy metabolism and fat accumulation.
Article
Nutrition & Dietetics
Orna Staretz-Chacham, Ben Pode-Shakked, Eyal Kristal, Smadar Yaala Abraham, Keren Porper, Ohad Wormser, Ilan Shelef, Yair Anikster
Summary: Partial KD treatment can improve the survival of patients with DLD-E3 deficiency, but it does not significantly improve the quality of life (QOL) of the patients.
Article
Chemistry, Medicinal
Xiaoguang Liu, Aimee A. Flores, Lisa Situ, Wen Gu, Hui Ding, Heather R. Christofk, William E. Lowry, Michael E. Jung
Summary: The study reports the synthesis and evaluation of novel UK-5099 analogues for potential treatment of hair loss, with certain compounds showing significant MPC inhibition activity and expanding chemical space for drug design. Some analogues were found to promote hair growth in mice when tested through topical treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Mohamed Touaibia, Patrick-Denis St-Coeur, Patrick Duff, Diene Codou Faye, Nicolas Pichaud
Summary: A series of thiazolidinediones were synthesized and studied for their effects on Drosophila melanogaster mitochondrial respiration. Compounds like 5-benzylidenethiazolidine-2,4-diones exhibited strong inhibitory capacity compared to other analogs, showing potential as potent mitochondrial pyruvate carrier inhibitors similar to UK5099. An analog, 5-benzylidenethiazolidine-2,4-dione 3, demonstrated positive effects on fruit fly survival and longevity, reversing the effects of a high fat diet and suggesting in vivo inhibition of MPC at the mitochondrial level.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Kyle S. McCommis, Brian N. Finck
Summary: Pyruvate is a crucial metabolic product that needs to be transported to the mitochondrial matrix for energy utilization or to become the building block of new biomolecules. The mitochondrial pyruvate carrier (MPC) has emerged as a target for therapeutic intervention in diseases related to altered mitochondrial and intermediary metabolism. In this review, the role of MPC and related metabolic pathways in the liver in regulating energy metabolism and the current state of targeting this pathway to treat liver diseases are discussed. Inhibiting MPC in hepatocytes and other liver cells has shown beneficial effects in treating type 2 diabetes and nonalcoholic steatohepatitis, although there are still gaps in our understanding of the pleiotropic effects of MPC inhibition.
Article
Microbiology
Raquel S. Negreiros, Noelia Lander, Miguel A. Chiurillo, Anibal E. Vercesi, Roberto Docampo
Summary: Pyruvate, the end product of glycolysis, is transported into the mitochondria through the mitochondrial pyruvate carriers MPC1 and MPC2. Knockout of MPC1 and MPC2 in Trypanosoma cruzi affects pyruvate-driven respiration, host cell invasion, and intracellular replication of amastigotes.
Article
Biochemistry & Molecular Biology
Xia Fang, Pei Zhao, Shaoyong Gao, Dongmei Liu, Song Zhang, Mengtian Shan, Yuanyuan Wang, Joerg Herrmann, Qiang Li, Feilong Wang
Summary: Tumor cell-derived lactate has been identified as the main factor in the polarization of tumor-associated macrophages (TAMs). Previous studies have highlighted the importance of mitochondrial pyruvate carrier (MPC)-mediated transport in TAMs polarization. However, our genetic depletion study demonstrated that MPC is not necessary for lactate-induced macrophages polarization or tumor growth.It also had no impact on the stabilization of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and histone lactylation, which are both crucial for TAMs polarization. This suggests that lactate itself, rather than its downstream metabolites, is responsible for TAMs polarization.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Chunlong Mu, Thomas A. Tompkins, Jong M. Rho, Morris H. Scantlebury, Jane Shearer
Summary: A growing body of evidence suggests that the gut microbiota plays an important role in regulating physiological processes, particularly through the gut-brain axis to modulate neural function and metabolism. This study reveals that manipulating the gut microbiota through diet, antibiotics, and probiotics has the potential to enhance brain mitochondrial function, which could be a novel strategy for treating epileptic disorders.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Medicine, Research & Experimental
Jiyoung Oh, Chungmo Koo, Kyung Won Kim, Jin-Sung Lee
Summary: PDH deficiency is an inherited metabolic disorder caused by a defect in the pyruvate dehydrogenase complex, with stress-induced gluconeogenesis potentially contributing to rapid disease exacerbation.
MEDICAL HYPOTHESES
(2021)
Article
Nutrition & Dietetics
Zeyu Zhou, Jocelyn Vidales, Jose A. Gonzalez-Reyes, Bradley Shibata, Keith Baar, Jennifer M. Rutkowsky, Jon J. Ramsey
Summary: The study found that a short-term ketogenic diet increased mitochondrial content in the red gastrocnemius muscle, but did not alter mitochondrial content in the liver, prefrontal cortex, or hippocampus. These results indicate tissue-specific changes in mitochondrial mass with a ketogenic diet.
Review
Biochemistry & Molecular Biology
Zandra Overgaard Pedersen, Sonja Holm-Yildiz, Tina Dysgaard
Summary: Ketogenic diet can reduce seizure frequency in patients with intractable epilepsy, but may induce liver impairment in patients with pathogenic POLG variants. Further research is needed due to limited evidence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Lourdes Sainero-Alcolado, Judit Liano-Pons, Maria Victoria Ruiz-Perez, Marie Arsenian-Henriksson
Summary: The research field of cancer metabolism has been based on the Warburg effect for decades, but recently the key role of mitochondria in cancer development has been demonstrated. Mutations in oncogenes, tumor suppressor genes, and metabolic enzymes alter various mitochondrial pathways in tumors, leading to metabolic reprogramming that sustains rapid cell proliferation and the utilization of reactive oxygen species by cancer cells. The knowledge acquired on mitochondrial cancer metabolism is now being translated into clinical practice, where detailed analysis of tumors is necessary to develop more precise treatments. Drugs targeting metabolic mitochondrial enzymes have shown potential in precision medicine, but efficient personalized drugs remain challenging to develop and may require combination with other strategies.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Guglielmina Chimienti, Antonella Orlando, Angela Maria Serena Lezza, Benedetta D'Attoma, Maria Notarnicola, Isabella Gigante, Vito Pesce, Francesco Russo
Summary: The study suggests that a ketogenic diet can reduce inflammation and oxidative stress, restore mitochondrial function and baseline autophagy by regulating the PPAR-gamma/PGC-1 alpha axis, which is effective in alleviating gut mitochondrial damage caused by stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Pallavi Subramanian, Sofia Gargani, Alessandra Palladini, Margarita Chatzimike, Michal Grzybek, Mirko Peitzsch, Anastasios D. Papanastasiou, Iryna Pyrina, Vasileios Ntafis, Bettina Gercken, Mathias Lesche, Andreas Petzold, Anupam Sinha, Marina Nati, Veera Raghavan Thangapandi, Ioannis Kourtzelis, Margarita Andreadou, Anke Witt, Andreas Dahl, Ralph Burkhardt, Robert Haase, Antonio Miguel de Jesus Domingues, Ian Henry, Nicola Zamboni, Peter Mirtschink, Kyoung-Jin Chung, Jochen Hampe, Unal Coskun, Dimitris L. Kontoyiannis, Triantafyllos Chavakis
Summary: The study found that hepatocyte-specific deficiency of HuR led to increased susceptibility to hepatic steatosis and fibrosis, as well as exacerbated inflammation, fibrosis, and HCC development on an NAFLD-inducing diet. The findings suggest that HuR plays a crucial role in maintaining liver homeostasis and preventing NAFLD-related fibrosis and HCC, indicating its potential therapeutic implications.
Article
Biochemistry & Molecular Biology
Kerstin Dorner, Lukas Badertscher, Bianka Horvath, Reka Hollandi, Csaba Molnar, Tobias Fuhrer, Roger Meier, Marie Sarazova, Jasmin van den Heuvel, Nicola Zamboni, Peter Horvath, Ulrike Kutay
Summary: Ribosome assembly is a crucial process in human cells and is related to congenital diseases and tumorigenesis. This study identified a group of factors involved in 60S subunit assembly in human cells and revealed the connections between 60S subunit maturation and other cellular processes. Additionally, the study discovered a novel function for polyamines in living cells in supporting ribosome synthesis.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Evan G. Williams, Niklas Pfister, Suheeta Roy, Cyril Statzer, Jack Haverty, Jesse Ingels, Casey Bohl, Moaraj Hasan, Jelena Cuklina, Peter Buhlmann, Nicola Zamboni, Lu Lu, Collin Y. Ewald, Robert W. Williams, Ruedi Aebersold
Summary: We analyzed the liver transcriptome, proteome, and metabolome of BXD mice to study the effects of diet and aging on molecular variations and metabolic traits. We identified genes associated with longevity and found common diet-related candidate genes across datasets. Our study provides insights into causal connections between diet, aging, and metabolic traits.
Article
Biochemical Research Methods
Michael A. Stravs, Kai Duehrkop, Sebastian Boecker, Nicola Zamboni
Summary: MSNovelist is a method that combines fingerprint prediction with an encoder-decoder neural network to generate de novo structures of small molecules from mass spectra. It demonstrates good predictive performance and achieves high accuracy and recovery rates even for unknown compounds.
Article
Biochemistry & Molecular Biology
Haibin Deng, Yanyun Gao, Verdiana Trappetti, Damian Hertig, Darya Karatkevich, Tereza Losmanova, Christian Urzi, Huixiang Ge, Gerrit Adriaan Geest, Remy Bruggmann, Valentin Djonov, Jean-Marc Nuoffer, Peter Vermathen, Nicola Zamboni, Carsten Riether, Adrian Ochsenbein, Ren-Wang Peng, Gregor Jan Kocher, Ralph Alexander Schmid, Patrick Dorn, Thomas Michael Marti
Summary: The study reveals the crucial role of lactate dehydrogenase B (LDHB) in regulating glucose and mitochondrial metabolism, and its impact on the survival and proliferation of non-small cell lung cancer (NSCLC) cells.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Jeremiah Bernier-Latmani, Cristina Mauri, Rachel Marcone, Francois Renevey, Stephan Durot, Liqun He, Michael Vanlandewijck, Catherine Maclachlan, Suzel Davanture, Nicola Zamboni, Graham W. Knott, Sanjiv A. Luther, Christer Betsholtz, Mauro Delorenzi, Cathrin Brisken, Tatiana Petrova
Summary: The specialized structure of small intestinal villus tip blood vessels is maintained by ADAMTS18(+) telocytes, which regulate the level and location of VEGFA signaling to ensure the presence of endothelial fenestrae for nutrient absorption, while avoiding excessive leakiness and destabilization of villus tip epithelial structures.
NATURE COMMUNICATIONS
(2022)
Article
Food Science & Technology
L. Ferreira Azevedo, M. Miguel Masiero, S. Cherkaoui, M. F. Hornos Carneiro, F. Barbosa, N. Zamboni
Summary: This study reveals that Bisphenol S (BPS) also disrupts molecular functions in cells that regulate energy homeostasis, displaying similar but less pronounced responses than Bisphenol A (BPA). Experiments on hepatocarcinoma and insulinoma cells demonstrate that exposure to BPA and BPS at different doses and durations have varying effects on cell growth and viability.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Immunology
Alejandra Gonzalez-Loyola, Jeremiah Bernier-Latmani, Irena Roci, Tania Wyss, Jakob Langer, Stephan Durot, Olivia Munoz, Borja Prat-Luri, Mauro Delorenzi, Matthias P. Lutolf, Nicola Zamboni, Gregory Verdeil, Tatiana Petrova
Summary: The transcription factor c-MAF plays a crucial role in regulating the differentiation and nutrient absorption in intestinal epithelial cells. Inactivation of c-MAF affects lipid handling, tuft cell expansion, and adaptive gut lengthening. These findings highlight the importance of the crosstalk between enterocytes and tuft cells in intestinal adaptation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Oncology
Ossia M. Eichhoff, Corinne I. Stoffel, Jan Kasler, Luzia Briker, Patrick Turko, Gergely Karsai, Nina Zila, Verena Paulitschke, Phil F. Cheng, Alexander Leitner, Andrea Bileck, Nicola Zamboni, Anja Irmisch, Zsolt Balazs, Aizhan Tastanova, Susana Pascoal, Pal Johansen, Rebekka Wegmann, Julien Mena, Alaa Othman, Vasanthi S. Viswanathan, Judith Wenzina, Andrea Aloia, Annalisa Saltari, Andreas Dzung, Michael Krauthammer, Stuart L. Schreiber, Thorsten Hornemann, Martin Distel, Berend Snijder, Reinhard Dummer, Mitchell P. Levesque
Summary: The clinical management of NRAS-mutated melanomas is challenging due to resistance that arises through genetic, transcriptional, and metabolic adaptation. However, the adoption of a mesenchymal phenotype with a quiescent metabolic program in NRAS-mutated melanoma cells confers sensitivity to reactive oxygen species (ROS) induction, which can be inhibited by ROS inducers in combination with MAPK pathway inhibitors. The findings suggest that targeting both metabolic reprogramming and MAPK signaling could improve patient treatment in melanoma and other cancers.
Review
Biochemistry & Molecular Biology
Timothy M. D. Ebbels, Justin J. J. van der Hooft, Haley Chatelaine, Corey Broeckling, Nicola Zamboni, Soha Hassoun, Ewy A. Mathe
Summary: The computational metabolomics field brings together experts from various disciplines to maximize the impact of metabolomics research. Advances in technology have generated complex datasets that require processing, annotation, modeling, and interpretation. Techniques for visualization, integration, and interpretation of metabolomics data have evolved alongside the development of databases and knowledge resources. This review highlights recent advances and discusses opportunities and innovations in response to challenges in the field.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Article
Endocrinology & Metabolism
Anand Kumar Sharma, Tongtong Wang, Alaa Othman, Radhika Khandelwal, Miroslav Balaz, Salvatore Modica, Nicola Zamboni, Christian Wolfrum
Summary: Emerging evidence suggests the existence of constant basal lipolysis and re-esterification of fatty acids. In this study, the role of lipolysis coupled to re-esterification under basal conditions was investigated. The results showed that DGAT1 and DGAT2 mediated re-esterification plays a role in regulating fatty acid oxidation and mitochondrial fuel utilization.
MOLECULAR METABOLISM
(2023)
Article
Multidisciplinary Sciences
Francesco Petrelli, Valentina Scandella, Sylvie Montessuit, Nicola Zamboni, Jean-Claude Martinou, Marlen Knobloch
Summary: Cellular metabolism plays a crucial role in the behavior of adult neural stem/progenitor cells (NSPCs). The mitochondrial pyruvate carrier (MPC) is identified as an important factor in controlling NSPC quiescence and activation.
Article
Endocrinology & Metabolism
Karin H. U. Meier, Julian Trouillon, Hai Li, Melanie Lang, Tobias Fuhrer, Nicola Zamboni, Shinichi Sunagawa, Andrew J. Macpherson, Uwe Sauer
Summary: Anatomically resolved maps of small molecules reveal distinct spatial patterns throughout the gut of colonized and germ-free mice, which can be associated with specific microorganisms. The map of the longitudinal metabolome in the gut of healthy mice shows a shift from amino acids to organic acids, vitamins, and nucleotides along the gut. Comparisons between colonized and germ-free mice help identify the origin of metabolites and suggest specific microbial influence on the metabolome.
Article
Biochemical Research Methods
Andrei Dmitrenko, Michelle Reid, Nicola Zamboni
Summary: We propose a new method, RALPS, for the normalization of multi-batch untargeted metabolomics data using deep adversarial learning. RALPS outperforms six state-of-the-art methods for batch correction, preserving biological identity, spectral properties, and coefficients of variation. It demonstrates good scalability, robustness, ability to handle missing values, and adaptability to different experimental designs.