Glucose-dependent control of leucine metabolism by leucyl-tRNA synthetase 1

Yoon, Ina; Nam, Miso; Kim, Hoi Kyoung; Moon, Hee Sun; Kim, Sung-Min; Jang, Jayun; Song, Ji Ae; Jeong, Seung Jae; Kim, Sang Bum; Cho, Seong-Min; Kim, Youn Ha; Lee, Jihye; Yang, Won-Mo; Yoo, Hee Chan; Kim, Ki-Bum; Kim, Min Sun; Yang, Aerin; Cho, Kyukwang; Park, Hee Sung; Hwang, Gwi Seo; Hwang, Kwang Yeon; Han, Jung Min; Kim, Jong Hyun; Kim, Sung‐Hoon

doi:10.1126/science.aau2753

Cited by 59 publications

(37 citation statements)

References 33 publications

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“…Other mechanistic links between mTORC2 and protein synthesis are conceivable. For instance, previous studies have reported that mTORC2 inhibition with Rictor mKO attenuated insulin/glucose-induced muscle glucose uptake (Kumar et al 2008;Kleinert et al 2014), and recent studies have shown that the availability of glucose in cells positively regulates protein synthesis (Kang et al 2019;Yoon et al 2020). Therefore, HK2 reduction in Rictor mKO mice, which probably reduced glucose metabolism, could also have contributed to reduced feeding-induced muscle protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

Rapamycin and mTORC2 inhibition synergistically reduce contraction‐stimulated muscle protein synthesis

Ogasawara

Knudsen

et al. 2020

The Journal of Physiology

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Muscle contractions increase protein synthesis in a mechanistic target of rapamycin (mTOR)-dependent manner, yet it is unclear which/how mTOR complexes regulate muscle protein synthesis. r We investigated the requirement of mTOR Complex 2 (mTORC2) in contraction-stimulated muscle protein synthesis. r mTORC2 inhibition by muscle-specific Rictor knockout (Rictor mKO) did not prevent contraction-induced muscle protein synthesis. r Rapamycin prevented contraction-induced muscle protein synthesis in Rictor mKO but not wild-type mice.

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Section: Discussionmentioning

confidence: 99%

Rapamycin and mTORC2 inhibition synergistically reduce contraction‐stimulated muscle protein synthesis

Ogasawara

Knudsen

et al. 2020

The Journal of Physiology

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“…Yoon et al found that in the absence of glucose, the unc-51 like autophagy activating kinase 1 (ULK1) phosphorylates LARS1 to reduce its binding to leucine, induce its detachment from the lysosomal membranes, and reduce its interaction with RagD, together leading to the inhibition of mTORC1 (Fig. 2), and promotion of leucine catabolism toward ATP generation 26 . Intriguingly, glucose deprivation-induced ULK1 phosphorylation is in part AMPK dependent and previous studies showed that ULK1 is a target of both AMPK and mTORC1 (refs.…”

Section: Ulk1 and The Trna Synthetase Lars1mentioning

confidence: 99%

How does mTOR sense glucose starvation? AMPK is the usual suspect

Leprivier

Rotblat

2020

Cell Death Discov.

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Glucose is a major requirement for biological life. Its concentration is constantly sensed at the cellular level, allowing for adequate responses to any changes of glucose availability. Such responses are mediated by key sensors and signaling pathway components that adapt cellular metabolism to glucose levels. One of the major hubs of these responses is mechanistic target of rapamycin (mTOR) kinase, which forms the mTORC1 and mTORC2 protein complexes. Under physiological glucose concentrations, mTORC1 is activated and stimulates a number of proteins and enzymes involved in anabolic processes, while restricting the autophagic process. Conversely, when glucose levels are low, mTORC1 is inhibited, in turn leading to the repression of numerous anabolic processes, sparing ATP and antioxidants. Understanding how mTORC1 activity is regulated by glucose is not only important to better delineate the biological function of mTOR, but also to highlight potential therapeutic strategies for treating diseases characterized by deregulated glucose availability, as is the case of cancer. In this perspective, we depict the different sensors and upstream proteins responsible of controlling mTORC1 activity in response to changes in glucose concentration. This includes the major energy sensor AMP-activated protein kinase (AMPK), as well as other independent players. The impact of such modes of regulation of mTORC1 on cellular processes is also discussed. Facts

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“…In addition, leucine has been shown to reduce fat deposition in mice [117] and there is the contention that leucine plays a regulatory role in fat reduction [117]. Interestingly, there are interactions between leucine and glucose, and the glucose status may determine whether leucine is used in protein synthesis or for energy production [118,119]. Thus, the potential capacity of leucine to promote protein synthesis but supress fat deposition is of immediate relevance to the development of reduced-CP diets for broiler chickens.…”

Section: Apparent Digestibility Coefficientmentioning

confidence: 99%

Synthetic and Crystalline Amino Acids: Alternatives to Soybean Meal in Chicken-Meat Production

Selle

Dorigam

Lemme

et al. 2020

Animals

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Simple Summary: There is a distinct possibility that synthetic and crystalline, or non-bound, amino acids will partially replace soybean meal in diets for broiler chickens and reduce the dependency of the chicken-meat industry on soybean meal as its principal source of protein.The genesis of this partial replacement will be the successful development of reduced-crude protein diets. A reduced-crude protein diet contains less soybean meal, and therefore less crude protein, but an increased array of essential and even non-essential non-bound amino acids so that requirements are met. There are, however, several challenges to be overcome if reduced-crude protein diets are to be successfully developed and adopted.Abstract: This review explores the premise that non-bound (synthetic and crystalline) amino acids are alternatives to soybean meal, the dominant source of protein, in diets for broiler chickens. Non-bound essential and non-essential amino acids can partially replace soybean meal so that requirements are still met but dietary crude protein levels are reduced. This review considers the production of non-bound amino acids, soybeans, and soybean meal and discusses the concept of reduced-crude protein diets. There is a focus on specific amino acids, including glycine, serine, threonine, and branched-chain amino acids, because they may be pivotal to the successful development of reduced-crude protein diets. Presently, moderate dietary crude protein reductions of approximately 30 g/kg are feasible, but more radical reductions compromise broiler performance. In theory, an 'ideal' amino acid profile would prevent this, but this is not necessarily the case in practice. The dependence of the chicken-meat industry on soybean meal will be halved if crude protein reductions in the order of 50 g/kg are attained without compromising the growth performance of broiler chickens. In this event, synthetic and crystalline, or non-bound, amino acids will become viable alternatives to soybean meal in chicken-meat production.Animals 2020, 10, 729 2 of 20 generates 1.1 kg CO 2 equivalents, which is considerably less than that of pork (3.8 kg CO 2 equivalents) or beef (14.8 kg CO 2 equivalents) production [2]. Moreover, it has been predicted that chicken-meat production will contribute 7.1% of greenhouse gas emissions compared to 29.8% and 63.1% for pork and beef, respectively [2]. However, diets for broiler chickens may contain more than 200 g/kg protein, the majority of which is derived from soybean meal; consequently, the chicken-meat industry has a huge demand for soybean meal. The production of 1 kg of chicken meat will require an input in the order of 560 g soybean meal given a conservative 250 g/kg dietary inclusion of soybean meal and a 2.25:1 conversion of feed into carcass weight. Importantly, this demand can be diminished by inclusions of non-bound (synthetic and crystalline) amino acids in broiler diets at the expense of soybean meal via the successful development of reduced-crude protein (CP) diets [3]. Therefore, synthetic...

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Glucose-dependent control of leucine metabolism by leucyl-tRNA synthetase 1

Cited by 59 publications

References 33 publications

Rapamycin and mTORC2 inhibition synergistically reduce contraction‐stimulated muscle protein synthesis

Rapamycin and mTORC2 inhibition synergistically reduce contraction‐stimulated muscle protein synthesis

How does mTOR sense glucose starvation? AMPK is the usual suspect

Synthetic and Crystalline Amino Acids: Alternatives to Soybean Meal in Chicken-Meat Production

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