mTORC2: a multifaceted regulator of autophagy

Sun, Yanan; Qu, Taiqi; Luo, Junjie; An, Peng; Ren, Fazheng; Luo, Yongting; Li, Yixuan

doi:10.1186/s12964-022-00859-7

Cited by 17 publications

(7 citation statements)

References 91 publications

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“…mTORC1 regulates cell growth and metabolism, while mTORC2 mainly controls cell proliferation and survival by phosphorylating and activating Akt, which in turn promotes cell proliferation and growth by inhibiting the mTORC1 inhibitor TSC1/2 through phosphorylation [ 37 ]. In addition, mTORC2 can activate Rho, PKC, and SGK1 through phosphorylation, thereby regulating cytoskeleton tissue and improving cell survival [ 38 ]. Overall, zein peptides play a beneficial effect on C 2 C 12 cells through MAPK and mTOR/PI3K/Akt pathways, by promoting cytoskeletal protein synthesis and stimulating cell proliferation and survival.…”

Section: Discussionmentioning

confidence: 99%

Zein-Derived Peptides from Corn Promote the Proliferation of C2C12 Myoblasts via Crosstalk of mTORC1 and mTORC2 Signaling Pathways

Amin,

Yu,

et al. 2024

Foods

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Dietary protein supplementation has emerged as a promising strategy in combating sarcopenia. Furthermore, searching for alternatives of animal proteins has been a hot topic. The present study aimed to investigate the effects of zein peptides on C2C12 myoblasts and explore their potential molecular mechanisms. The proliferative, cell cycle, and anti-apoptotic activities of zein peptides were evaluated. Peptidomics analysis and transcriptome sequencing were employed to explore the structure-activity relationship and underlying molecular mechanisms. The results indicated that zein peptides (0.05–0.2 mg/mL) exerted a significant proliferation-promoting impact on C2C12 cells, via increasing cell viability by 33.37 to 42.39%. Furthermore, zein peptides significantly increased S phase proportion and decreased the apoptosis rate from 34.08% (model group) to 28.96% in C2C12 cells. In addition, zein peptides exhibited a pronounced anti-apoptotic effect on C2C12 cells. Zein peptides are abundant in branch-chain amino acids, especially leucine. Transcriptomics analysis revealed that zein peptides can promote proliferation, accelerate cell cycle, and improve protein synthesis of muscle cells through mTORC1 and mTORC2 signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Zein-Derived Peptides from Corn Promote the Proliferation of C2C12 Myoblasts via Crosstalk of mTORC1 and mTORC2 Signaling Pathways

Amin,

Yu,

et al. 2024

Foods

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“…Conversely, at low cell density, YAP1 translocates into the nucleus, activating the expression of actomyosin genes, which induces the formation of actin stress fibers and maintains YAP1 in the nucleus. The mechanical strain exerted on mesenchymal stem cells activates mTORC2, a regulator of autophagy that influences various downstream effectors [199]. This mechanical activation of mTORC2 can be prevented by pharmacological inhibition of focal adhesion kinase (FAK), which is mechanosensitive.…”

Section: Autophagy In Cip and Mechanotransductionmentioning

confidence: 99%

The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation

Nakamura

2024

IJMS

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Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing the formation of cancerous tissues. CI can be further categorized into two distinct yet interrelated components: CI of locomotion (CIL) and CI of proliferation (CIP). These two components of CI have historically been viewed as separate processes, but emerging research suggests that they may be regulated by both distinct and shared pathways. Specifically, recent studies have indicated that both CIP and CIL utilize mechanotransduction pathways, a process that involves cells sensing and responding to mechanical forces. This review article describes the role of mechanotransduction in CI, shedding light on how mechanical forces regulate CIL and CIP. Emphasis is placed on filamin A (FLNA)-mediated mechanotransduction, elucidating how FLNA senses mechanical forces and translates them into crucial biochemical signals that regulate cell locomotion and proliferation. In addition to FLNA, trans-acting factors (TAFs), which are proteins or regulatory RNAs capable of directly or indirectly binding to specific DNA sequences in distant genes to regulate gene expression, emerge as sensitive players in both the mechanotransduction and signaling pathways of CI. This article presents methods for identifying these TAF proteins and profiling the associated changes in chromatin structure, offering valuable insights into CI and other biological functions mediated by mechanotransduction. Finally, it addresses unanswered research questions in these fields and delineates their possible future directions.

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“…Here, we will only consider mTORC1 in the regulation of autophagy by amino acids and insulin. Nevertheless, mTORC2 can also affect autophagy (reviewed in Refs [71,72]). Amino acids and insulin signaling act on different components of mTORC1 [16] (Fig.…”

Section: Pioneering Discoveriesmentioning

confidence: 99%

A historical perspective of macroautophagy regulation by biochemical and biomechanical stimuli

Dupont,

Claude‐Taupin,

Codogno

2023

FEBS Letters

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Macroautophagy is a lysosomal degradative pathway for intracellular macromolecules, protein aggregates and organelles. The formation of the autophagosome, a double membrane‐bound structure that sequesters cargoes before their delivery to the lysosome, is regulated by several stimuli in multicellular organisms. Pioneering studies in rat liver showed the importance of amino acids, insulin and glucagon in controlling macroautophagy. Thereafter, many studies have deciphered the signaling pathways downstream of these biochemical stimuli to control autophagosome formation. Two signaling hubs have emerged: the kinase mTOR, in a complex at the surface of lysosomes which is sensitive to nutrients and hormones; and AMPK, which is sensitive to the cellular energetic status. Besides nutritional, hormonal and energetic fluctuations, many organs have to respond to mechanical forces (compression, stretching and shear stress). Recent studies have shown the importance of mechanotransduction in controlling macroautophagy. This regulation engages cell surface sensors, such as the primary cilium, in order to translate mechanical stimuli into biological responses.

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mTORC2: a multifaceted regulator of autophagy

Cited by 17 publications

References 91 publications

Zein-Derived Peptides from Corn Promote the Proliferation of C2C12 Myoblasts via Crosstalk of mTORC1 and mTORC2 Signaling Pathways

Zein-Derived Peptides from Corn Promote the Proliferation of C2C12 Myoblasts via Crosstalk of mTORC1 and mTORC2 Signaling Pathways

The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation

A historical perspective of macroautophagy regulation by biochemical and biomechanical stimuli

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