Article
Nutrition & Dietetics
Amber Berdenis van Berlekom, Raphael Kubler, Jeske W. Hoogeboom, Danielle Vonk, Jacqueline A. Sluijs, R. Jeroen Pasterkamp, Jinte Middeldorp, Aletta D. Kraneveld, Johan Garssen, Rene S. Kahn, Elly M. Hol, Lot D. de Witte, Marco P. Boks
Summary: There is compelling evidence that nutrition has a significant impact on human brain development. Previous studies have shown that three specific amino acids, histidine, lysine, and threonine, can synergistically inhibit mTOR activity and behavior. In this pioneering study, human cerebral organoids were used to investigate the impact of amino acid supplementation on neurodevelopment. The results showed that exposure to threonine, histidine, and lysine led to decreased mTOR activity, reduced organoid size, and altered gene expression, supporting findings from previous rodent studies.
Article
Biochemistry & Molecular Biology
Yuna Amemiya, Nao Nakamura, Nao Ikeda, Risa Sugiyama, Chiaki Ishii, Masatoshi Maki, Hideki Shibata, Terunao Takahara
Summary: The study reveals that amino acids converge on regulating the TSC2-Rheb axis via Ca2+/calmodulin to increase mTORC1 activity and promote nascent protein synthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Jason S. Shapiro, Hsiang-Chun Chang, Yuki Tatekoshi, Zibo Zhao, Zohra Sattar Waxali, Bong Jin Hong, Haimei Chen, Justin A. Geier, Elizabeth T. Bartom, Adam De Jesus, Farnaz K. Nejad, Amir Mahmoodzadeh, Tatsuya Sato, Lucia Ramos-Alonso, Antonia Maria Romero, Maria Teresa Martinez-Pastor, Shang-Chuan Jiang, Shiv K. Sah-Teli, Liming Li, David Bentrem, Gary Lopaschuk, Issam Ben-Sahra, Thomas V. O'Halloran, Ali Shilatifard, Sergi Puig, Joy Bergelson, Peppi Koivunen, Hossein Ardehali
Summary: The study reveals a previously undescribed iron sensing pathway in eukaryotic cells, in which the iron-binding histone demethylase KDM3B acts as an intrinsic iron sensor to regulate mTORC1 activity and maintain the expression of critical components of the pathway.
NATURE CELL BIOLOGY
(2023)
Review
Cell Biology
Michaela E. Trautman, Nicole E. Richardson, Dudley W. Lamming
Summary: The proportion of people suffering from age-related diseases is increasing worldwide. Recent research has shown that low protein diets, particularly those low in branched-chain amino acids (BCAAs), can reduce mortality and promote metabolic health and extended lifespan in both humans and rodents. This article discusses the emerging evidence that BCAAs play a crucial role in healthy metabolism and longevity, and explores the physiological and molecular mechanisms behind the benefits of restricting dietary BCAAs. The findings suggest that the quality of protein, specifically the composition of dietary protein, may be a previously overlooked factor in metabolic dysfunction and reducing dietary BCAAs could be a promising new approach to delaying and preventing age-related diseases.
Article
Agriculture, Dairy & Animal Science
Marta Vazquez-Gomez, Consolacion Garcia-Contreras, Susana Astiz, Laura Torres-Rovira, Jose Luis Pesantez-Pacheco, Ana Heras-Molina, Teresa Castro Madrigal, Clemente Lopez-Bote, Cristina Ovilo, Antonio Gonzalez-Bulnes, Beatriz Isabel
Summary: Nutritional strategies during pregnancy, such as amino acid supplementation with glutamine, are important for improving swine production outcomes. However, the effects of prenatal supplementation on traditional swine breeds, such as Iberian pigs, are complex and require further research to fully understand and optimize their outcomes.
Article
Biochemistry & Molecular Biology
Sung Eun Kim, Justin Zhang, Enoch Jiang, Michael Overholtzer
Summary: Metabolic stress plays a role in regulating cell death, with amino acid signaling and the mTOR-4E-BP1/2 pathway identified as an upstream regulation mechanism for the fate of live engulfed cells formed by entosis and HoCC. Amino acid withdrawal or mTOR inhibition induces apoptosis of engulfed cells and blocks entotic cell death that is associated with the lipidation of the autophagy protein LC3.
Article
Pediatrics
Marko Rudar, Jane K. K. Naberhuis, Agus Suryawan, Hanh V. Nguyen, Marta L. L. Fiorotto, Teresa A. A. Davis
Summary: Prematurity independently contributes to the blunted postprandial protein synthesis, which may lead to slow growth and reduced lean mass in premature infants.
PEDIATRIC RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Jehad Z. Tayyeb, Herman E. Popeijus, Janna van de Sanden, Willem Zwaan, Ronald P. Mensink, Jogchum Plat
Summary: Individual amino acids have different effects on ApoA-I mRNA expression and pro-ApoA-I protein production. Leucine, glutamic acid, and tryptophan can increase ApoA-I and CPT1 mRNA expression, while tryptophan also enhances PPAR alpha transactivation. Glutamine, proline, and histidine can increase pro-ApoA-I protein concentrations, but mTORC1 phosphorylation remains unchanged regardless of the amino acid provided.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Andres Norambuena, Xuehan Sun, Horst Wallrabe, Ruofan Cao, Naidi Sun, Evelyn Pardo, Nutan Shivange, Dora Bigler Wang, Lisa A. Post, Heather A. Ferris, Song Hu, Ammasi Periasamy, George S. Bloom
Summary: This study reveals a novel mechanism of mitochondrial DNA synthesis in Alzheimer's disease, where nutrient-stimulated lysosomal mTORC1 activity regulates mtDNA replication in neurons. The study also shows a link between tau and superoxide dismutase 1 (SOD1) to mitochondrial dysfunction and Alzheimer's disease.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Tetsuya Kimura, Yoshitomo Hayama, Daisuke Okuzaki, Shigeyuki Nada, Masato Okada
Summary: mTORC1 signaling pathway plays a crucial role in regulating cellular responses. This study demonstrates that Ragulator complex is essential for inhibiting the nuclear translocation of TFEB, and mTORC1 requires Ragulator for regulating the subcellular distribution of TFEB.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Nutrition & Dietetics
Evasio Pasini, Giovanni Corsetti, Francesco Saverio Dioguardi
Summary: Chronic heart failure (CHF) remains a major health problem in industrialized countries, despite therapeutic improvements. Malnutrition, especially protein energy malnutrition, is present in more than half of CHF patients and is an independent predictor of prognosis. Nutritional supplementation and exercise training have been used to treat this condition, but their effectiveness is inconclusive. This paper discusses the molecular mechanisms of specific nutritional supplementation and exercise training that may improve anabolic pathways, particularly focusing on the relationship between exercise and the mTOR complex subunit as Deptor and/or related signaling proteins.
Article
Biochemistry & Molecular Biology
Meiling Lu, Lei Yu, Yanrong Yang, Jiali Zhu, Sujing Qiang, Xinbo Wang, Jia Wang, Xiao Tan, Weifeng Wang, Yue Zhang, Weichao Wang, Jian Xie, Xinyan Chen, Hongbing Wang, Xianghuan Cui, Xin Ge
Summary: The study identifies hayatine as a potential mTORC1 inhibitor with unique properties that can suppress cancer cell growth through various mechanisms, offering promise in overcoming rapamycin resistance for cancer treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Cell Biology
Mariana Borsa, Sandrine Obba, Felix C. Richter, Hanlin Zhang, Thomas Riffelmacher, Joana Carrelha, Ghada Alsaleh, Sten Eirik W. Jacobsen, Anna Katharina Simon
Summary: This study investigates the importance of autophagy in stem cells and finds that autophagy deficiency leads to stem cell loss and bone marrow failure, while inhibition of MTOR can rescue this loss and improve stem cell function.
Editorial Material
Cell Biology
Tomoyuki Fukuda, Kazuhiro Shiozaki
Summary: The GATOR2 component Sea3 in fission yeast unexpectedly acts as part of GATOR1 to suppress TORC1. In fission yeast, GATOR1 is not required for amino acid starvation-induced TORC1 attenuation, which is mediated by the Gcn2 pathway. Absence of a nitrogen source suppresses TORC1 through GATOR1 and the Tsc1-Tsc2 complex.
Article
Multidisciplinary Sciences
Xin Gu, Patrick Jouandin, Pranav Lalgudi, Rich Binari, Max L. Valenstein, Michael A. Reid, Annamarie E. Allen, Nolan Kamitaki, Jason W. Locasale, Norbert Perrimon, David M. Sabatini
Summary: Flies can sense and detect a diet deficient in essential amino acid leucine through the nutrient sensing of mTORC1 signaling.