Amino Acid Signaling for TOR in Eukaryotes: Sensors, Transducers, and a Sustainable Agricultural fuTORe

Lutt, Nanticha; Brunkard, Jacob O.

doi:10.3390/biom12030387

Cited by 16 publications

(9 citation statements)

References 110 publications

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“…Sestrin 2-GATOR2-GATOR1-RagB signaling mediates the stress-dependent suppression of mTORC1 activity [ 394 ]. Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling [ 395 ] and regulate the localization of mTORC1 in response to amino acids [ 396 , 397 ].…”

Section: Perinatal Factors Disturbing Mex Mir-regulated β Cell Homeos...mentioning

confidence: 99%

Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life

Melnik

Schmitz

2022

IJMS

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Pancreatic β cell expansion and functional maturation during the birth-to-weaning period is driven by epigenetic programs primarily triggered by growth factors, hormones, and nutrients provided by human milk. As shown recently, exosomes derived from various origins interact with β cells. This review elucidates the potential role of milk-derived exosomes (MEX) and their microRNAs (miRs) on pancreatic β cell programming during the postnatal period of lactation as well as during continuous cow milk exposure of adult humans to bovine MEX. Mechanistic evidence suggests that MEX miRs stimulate mTORC1/c-MYC-dependent postnatal β cell proliferation and glycolysis, but attenuate β cell differentiation, mitochondrial function, and insulin synthesis and secretion. MEX miR content is negatively affected by maternal obesity, gestational diabetes, psychological stress, caesarean delivery, and is completely absent in infant formula. Weaning-related disappearance of MEX miRs may be the critical event switching β cells from proliferation to TGF-β/AMPK-mediated cell differentiation, whereas continued exposure of adult humans to bovine MEX miRs via intake of pasteurized cow milk may reverse β cell differentiation, promoting β cell de-differentiation. Whereas MEX miR signaling supports postnatal β cell proliferation (diabetes prevention), persistent bovine MEX exposure after the lactation period may de-differentiate β cells back to the postnatal phenotype (diabetes induction).

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Section: Perinatal Factors Disturbing Mex Mir-regulated β Cell Homeos...mentioning

confidence: 99%

Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life

Melnik

Schmitz

2022

IJMS

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“…One major way of amino acid signaling is mediated by amino acid-binding proteins, including enzymes, transporters, tRNA ( 112 ). For instance, target of rapamycin was recently reported to be activated by amino acids ( 116 ). As such, Ding et al demonstrated that amino acids could function as specific and selective signaling molecules ( 117 ).…”

Section: Amino Acids As Signaling Molecules In T Cellsmentioning

confidence: 99%

Immunometabolism – The Role of Branched-Chain Amino Acids

Yahsi

Günaydın

2022

Front. Immunol.

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Immunometabolism has been the focus of extensive research over the last years, especially in terms of augmenting anti-tumor immune responses. Regulatory T cells (Tregs) are a subset of CD4+ T cells, which have been known for their immunosuppressive roles in various conditions including anti-tumor immune responses. Even though several studies aimed to target Tregs in the tumor microenvironment (TME), such approaches generally result in the inhibition of the Tregs non-specifically, which may cause immunopathologies such as autoimmunity. Therefore, specifically targeting the Tregs in the TME would be vital in terms of achieving a successful and specific treatment. Recently, an association between Tregs and isoleucine, which represents one type of branched-chain amino acids (BCAAs), has been demonstrated. The presence of isoleucine seems to affect majorly Tregs, rather than conventional T cells. Considering the fact that Tregs bear several distinct metabolic features in the TME, targeting their immunometabolic pathways may be a rational approach. In this Review, we provide a general overview on the potential distinct metabolic features of T cells, especially focusing on BCAAs in Tregs as well as in their subtypes.

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“…1). Although RAGs are conserved in mammals and yeast (Nicastro et al ., 2017; Liu & Sabatini, 2020), both transducers and the proposed AA sensors are missing in plants and green microalgae (Liu & Xiong, 2022; Lutt & Brunkard, 2022; Mallén‐Ponce et al ., 2022a), suggesting that nutrient availability is signaled to TORC1 in these organisms through different mechanism(s).…”

Section: Control Of Torc1 By Amino Acidsmentioning

confidence: 99%

Analyzing the impact of autotrophic and heterotrophic metabolism on the nutrient regulation of TOR

2022

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The target of rapamycin (TOR) protein kinase is a master regulator of cell growth in all eukaryotes, from unicellular yeast and algae to multicellular animals and plants. Target of rapamycin balances the synthesis and degradation of proteins, lipids, carbohydrates and nucleic acids in response to nutrients, growth factors and cellular energy to promote cell growth. Among nutrients, amino acids (AAs) and glucose are central regulators of TOR activity in evolutionary distant eukaryotes such as mammals, plants and algae. However, these organisms obtain the nutrients through totally different metabolic processes. Although photosynthetic eukaryotes can use atmospheric CO 2 as the sole carbon (C) source for all reactions in the cell, heterotrophic organisms get nutrients from other sources of organic C including glucose. Here, we discuss the impact of autotrophic and heterotrophic metabolism on the nutrient regulation of TOR, focusing on the role of AAs and C sources upstream of this signaling pathway.

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Amino Acid Signaling for TOR in Eukaryotes: Sensors, Transducers, and a Sustainable Agricultural fuTORe

Cited by 16 publications

References 110 publications

Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life

Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life

Immunometabolism – The Role of Branched-Chain Amino Acids

Analyzing the impact of autotrophic and heterotrophic metabolism on the nutrient regulation of TOR

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