Review
Biochemistry & Molecular Biology
Beatriz Pardo, Eduardo Herrada-Soler, Jorgina Satrustegui, Laura Contreras, Araceli del Arco
Summary: AGC1/Aralar is a mitochondrial carrier involved in the transfer of redox power in neurons. Deficiency in AGC1/Aralar leads to a rare human disease and affects both neuronal and glial functions, resulting in various pathophysiological changes related to neuronal metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Endocrinology & Metabolism
Melissa H. Broeks, Clara D. M. van Karnebeek, Ronald J. A. Wanders, Judith J. M. Jans, Nanda M. Verhoeven-Duif
Summary: The malate aspartate shuttle (MAS) is crucial for mitochondrial respiration and maintaining cytosolic redox balance, playing a key role in sustaining metabolic pathways like glycolysis and serine biosynthesis. Five potential MAS deficiencies have been reported, mostly presenting with infantile epileptic encephalopathy. Biochemical characteristics such as high lactate, disturbed redox balance, and low serine can aid in diagnosis, while treatment options include a ketogenic diet, serine, and vitamin B6 supplementation.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Milan Holecek
Summary: Aspartate-glutamate carrier 2 (AGC2) is a mitochondrial carrier that plays a crucial role in maintaining redox balance, mitochondrial respiration, and ATP synthesis. It is activated during starvation and muscle wasting disorders and is involved in the metabolism of aspartate and glutamate. Targeting AGC genes may offer a new therapeutic strategy against cancer.
Review
Biochemistry & Molecular Biology
Milan Holecek
Summary: Aspartate-glutamate carrier 2 (AGC2) is a mitochondrial carrier expressed in the liver that plays a crucial role in maintaining intracellular redox balance, mitochondrial respiration, and ATP synthesis. It is stimulated by catecholamines and glucagon during starvation, exercise, and muscle wasting disorders, and increases aspartate input to the urea cycle. Targeting AGC genes may provide a new therapeutic strategy to fight cancer.
Article
Genetics & Heredity
Luis Gonzalez-Moreno, Andrea Santamaria-Cano, Alberto Paradela, Maria Luz Martinez-Chantar, Miguel A. Martin, Mercedes Perez-Carreras, Alberto Garcia-Picazo, Jesus Vazquez, Enrique Calvo, Gloria Gonzalez-Aseguinolaza, Takeyori Saheki, Araceli del Arco, Jorgina Satrustegui, Laura Contreras
Summary: The deficiency of CITRIN, the liver mitochondrial aspartate-glutamate carrier (AGC), is the cause of four human clinical phenotypes. A potential therapy for this condition is the expression of aralar, the AGC present in brain, to replace citrin. To explore the significance of AGC replacement in human therapy, the relative levels of citrin and aralar in mouse and human liver were studied. The results support the benefit of increasing aralar expression to improve the redox balance capacity of human liver, as an effective therapy for CITRIN deficiency.
MOLECULAR GENETICS AND METABOLISM REPORTS
(2023)
Article
Microbiology
Fangying Li, Xiaozhe Fu, Xia Luo, Qiang Lin, Hongru Liang, Yinjie Niu, Lihui Liu, Ningqiu Li
Summary: Viruses rely on host cellular metabolism to complete their life cycle, and Siniperca chuatsi rhabdovirus (SCRV) has caused significant economic losses to the Chinese perch industry. This study investigated the role of asparagine metabolism in SCRV proliferation and found that key enzymes in the aspartate metabolic pathway were upregulated during SCRV infection. Addition of asparagine and glutamine restored SCRV replication, while inhibition of the aspartate-malate shuttle pathway and knockdown of key enzymes in the asparagine biosynthesis pathway reduced SCRV production. These findings provide insights into the pathogenic mechanism of SCRV through regulation of aspartate metabolism.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Endocrinology & Metabolism
Tobias Ackermann, Hidde R. Zuidhof, Christine Mueller, Gertrud Kortman, Martijn G. S. Rutten, Mathilde J. C. Broekhuis, Mohamad Amr Zaini, Gotz Hartleben, Cornelis F. Calkhoven
Summary: Cancer cells rely on glycolysis for energy production and growth. The transcription factor C/EBPλ-LIP promotes glycolysis and mitochondrial respiration in cancer cells. High expression of C/EBPλ-LIP increases vulnerability to glycolysis inhibition.
MOLECULAR METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Cuiyan Zhou, Wangsong Shang, Shan-Kai Yin, Haibo Shi, Weihai Ying
Summary: Our study revealed that aminooxyacetic acid (AOAA) inhibits LPS-induced neuroinflammation by modulating the malate-aspartate shuttle (MAS), suggesting AOAA as a new and effective drug. Furthermore, we found that MAS is a novel mediator of LPS-induced neuroinflammation due to its ability to modulate LPS-induced STAT3 phosphorylation, highlighting the critical role of NAD(+)/NADH metabolism in inflammation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Olivia Vazquez-Martinez, Mauricio Diaz-Munoz, Fernando Lopez-Barrera, Rolando Hernandez-Munoz
Summary: This study explored the impact of isoproterenol-induced myocardial damage on mitochondrial function, specifically focusing on the malate-aspartate shuttle activity. The results showed minimal effects on endogenous shuttle activity, but significant enhancement in a reconstituted system during the post-infarction period, suggesting a compensatory response of cardiomyocytes to the metabolic consequences of myocardial infarction. These findings highlight the sequential biochemical and metabolic modifications within cardiomyocytes during heart damage associated with myocardial infarction, emphasizing the potential role of mitochondrial activity in controlling the redox state.
Article
Neurosciences
Jens Andersen, Kia H. Markussen, Emil Jakobsen, Arne Schousboe, Helle S. Waagepetersen, Paul A. Rosenberg, Blanca Aldana
Summary: Glutamate plays a crucial role in brain function, with its recycling dependent on metabolic collaboration between neurons and astrocytes. In addition to its involvement in brain energy metabolism, glutamate also serves as a hub connecting glucose and amino acid metabolism, disruptions in which can lead to neuronal excitotoxicity. Understanding the regulation of glutamate-dependent metabolic processes may provide new insights and targets for treating neurodegenerative diseases.
Article
Biochemistry & Molecular Biology
Thibaut Molinie, Elodie Cougouilles, Claudine David, Edern Cahoreau, Jean-Charles Portais, Arnaud Mourier
Summary: The mitochondrial respiratory chain plays a crucial role in metabolic processes by regenerating NAD+ and ATP. Recent studies have shown that complex I can form functional entities called respirasomes, which facilitate NADH oxidation. However, findings demonstrate that complex II is preferred for electron transfer in heart and liver mitochondria. This unexpected result suggests a new regulatory mechanism for mitochondrial respiration in response to NADH/NAD+ redox stress.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2022)
Review
Biochemistry & Molecular Biology
Douglas L. Rothman, Kevin L. Behar, Gerald A. Dienel
Summary: The relationship between neuronal glucose oxidation and neurotransmitter cycling has been established, but the mechanism behind it is not fully understood. Understanding this mechanism is crucial for interpreting brain imaging studies. Several models have been proposed to explain the relationship, but they have limitations. Improved models have been developed to address these limitations and provide a better understanding of neurotransmission.
JOURNAL OF NEUROCHEMISTRY
(2022)
Review
Oncology
Thomas N. Seyfried, Gabriel Arismendi-Morillo, Giulio Zuccoli, Derek C. Lee, Tomas Duraj, Ahmed M. Elsakka, Joseph C. Maroon, Purna Mukherjee, Linh Ta, Laura Shelton, Dominic D'Agostino, Michael Kiebish, Christos Chinopoutos
Summary: Glioblastoma relies on fermentation metabolism for energy and biomass synthesis, contributing to an acidified microenvironment and drug resistance. Treatment methods for GBM can further acidify the microenvironment, but restricting glucose and glutamine while increasing non-fermentable ketone bodies may provide a non-toxic therapeutic strategy.
FRONTIERS IN ONCOLOGY
(2022)
Review
Nutrition & Dietetics
Milan Holecek
Summary: Aspartic acid exists in different isoforms and plays various roles in cellular processes, including protein synthesis, neurotransmission, and disease pathogenesis.
Article
Neurosciences
Irene Perez-Liebana, Ines Juaristi, Paloma Gonzalez-Sanchez, Luis Gonzalez-Moreno, Eduardo Rial, Masa Podunavac, Armen Zakarian, Jordi Molgo, Ainara Vallejo-Illarramendi, Laura Mosqueira-Martin, Adolfo Lopez de Munain, Beatriz Pardo, Jorgina Satrustegui, Araceli del Arco
Summary: Calcium acts as an important secondary messenger in regulating the bioenergetic response in neurons. In glucose-utilizing embryonic mouse cortical neurons, calcium upregulates glycolysis, pyruvate levels, and respiration through the Aralar-MAS pathway, while not affecting glucose uptake. This calcium-dependent pathway plays a key role in tuning both glycolysis and oxidative phosphorylation in response to neuronal activation.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Genetics & Heredity
Tommy Stodberg, Mans Magnusson, Nicole Lesko, Anna Wredenberg, Daniel Martin Munoz, Henrik Stranneheim, Anna Wedell
NEUROLOGY-GENETICS
(2020)
Article
Clinical Neurology
Sintia Kolbjer, Daniel A. Martin, Maria Pettersson, Maria Dahlin, Britt-Marie Anderlid
Summary: The most common genetic etiologies in a cohort of 20 individuals with epilepsy and lissencephaly spectrum were intragenic deletions or single nucleotide mutations in PAFAH1B1 or larger deletions in 17p13.3, encompassing PAFAH1B1, followed by mutations in tubulin encoding genes. Radiological findings could reliably predict molecular results only in agyria with a posterior to anterior gradient. However, radiological and molecular findings did not consistently correlate with severity of clinical outcome or therapeutic response.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2021)
Letter
Hematology
Jan-Inge Henter, Egle Kvedaraite, Daniel Martin Munoz, Monica Cheng Munthe-Kaas, Bernward Zeller, Tove A. Nystad, Caroline Bjorklund, Isabella Donner, Magda Lourda, Henrik Zetterberg, Kaj Blennow, Nikolas Herold, Desiree Gavhed, Tatiana von Bahr Greenwood
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Oncology
Urszula Arnljots, Maria Nilsson, Ulrika Sandvik, Ida Hed Myrberg, Daniel Martin Munoz, Klas Blomgren, Kerstin Hellgren
Summary: This study investigates the potential use of optical coherence tomography (OCT) in examining children with optic pathway glioma (OPG). The results show significant correlations between ganglion cell-inner plexiform layer (GC-IPL) thickness and visual function, and suggest that GC-IPL measures could serve as an early marker of vision loss related to OPG. These findings provide valuable insights for the clinical follow-up and treatment choices of OPG.
Article
Medicine, General & Internal
Giovanna Marchini, Daniel Martin Munoz, Ylva Vladic Stjernholm
CLINICAL CASE REPORTS
(2020)
Article
Medicine, Research & Experimental
Susan Blaser, Evan J. Propst, Daniel Martin, Annette Feigenbaum, Adrian L. James, Patrick Shannon, Blake C. Papsin