Dataset Information

Mechanical loading modulates AMPK and mTOR signaling in myoblasts

ABSTRACT: Skeletal muscle adaptation to exercise involves various phenotypic changes that enhance metabolic and contractile functions. One key regulator of these adaptive responses is the activation of AMPK, influenced by exercise intensity. However, the mechanistic understanding of AMPK activation during exercise remains incomplete. In this study, we utilized an in vitro model to investigate the effects of mechanical loading on AMPK activation and its interplay with the mTOR signaling pathway. Proteomic analysis of myoblasts subjected to static loading (SL) revealed distinct quantitative protein alterations associated with RNA metabolism, with 10% SL inducing the most pronounced response compared to lower intensity of 5% and 2% as well as control. Additionally, 10% SL suppressed RNA and protein synthesis, while activating AMPK and inhibiting the mTOR pathway. We also found that SRSF2, necessary for pre-mRNA splicing, is regulated by AMPK and mTOR signaling, which, in turn, is regulated in an intensity-dependent manner by SL with highest expression in 2% SL. Further examination showed that SL induced changes in mitochondrial biogenesis and the ADP/ATP ratio. These findings provide novel insights into the cellular responses to mechanical loading and shed light on the intricate AMPK-mTOR regulatory network in myoblasts.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Muscle Cell

SUBMITTER: Shaochun Zhu

LAB HEAD: Ludvig J. Backman

PROVIDER: PXD050925 | Pride | 2025-05-06

REPOSITORIES: Pride

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			Action	DRS
	S00001_Exploris01_AM_XinZhou_Ctrl_n1.raw	Raw
	S00002_Exploris01_AM_XinZhou_Ctrl_n2.raw	Raw
	S00003_Exploris01_AM_XinZhou_Ctrl_n3.raw	Raw
	S00004_Exploris01_AM_XinZhou_2perc_n1.raw	Raw
	S00005_Exploris01_AM_XinZhou_2perc_n2.raw	Raw

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Publications

Mechanical Loading Modulates AMPK and mTOR Signaling in Muscle Cells.

Zhou Xin X Zhu Shaochun S Li Junhong J Mateus Andre A Williams Chloe C Gilthorpe Jonathan J Backman Ludvig J LJ

Journal of proteome research 20240830 10

Skeletal muscle adaptation to exercise involves various phenotypic changes that enhance the metabolic and contractile functions. One key regulator of these adaptive responses is the activation of AMPK, which is influenced by exercise intensity. However, the mechanistic understanding of AMPK activation during exercise remains incomplete. In this study, we utilized an in vitro model to investigate the effects of mechanical loading on AMPK activation and its interaction with the mTOR signaling path ...[more]

PMID: 39213513

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Project description:DallePezze2016 - Activation of AMPK and mTOR by amino acids (Model 3) This model is as described in the Supplementary Software 3 of the reference publication: SBML model similar to Model S2, but including a more complex p70-S6K module. This model is described in the article: A systems study reveals concurrent activation of AMPK and mTOR by amino acids. Dalle Pezze P, Ruf S, Sonntag AG, Langelaar-Makkinje M, Hall P, Heberle AM, Razquin Navas P, van Eunen K, Tölle RC, Schwarz JJ, Wiese H, Warscheid B, Deitersen J, Stork B, Fäßler E, Schäuble S, Hahn U, Horvatovich P, Shanley DP, Thedieck K. Nat Commun 2016 Nov; 7: 13254 Abstract: Amino acids (aa) are not only building blocks for proteins, but also signalling molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a key mediator. However, little is known about whether aa, independently of mTORC1, activate other kinases of the mTOR signalling network. To delineate aa-stimulated mTOR network dynamics, we here combine a computational-experimental approach with text mining-enhanced quantitative proteomics. We report that AMP-activated protein kinase (AMPK), phosphatidylinositide 3-kinase (PI3K) and mTOR complex 2 (mTORC2) are acutely activated by aa-readdition in an mTORC1-independent manner. AMPK activation by aa is mediated by Ca2+/calmodulin-dependent protein kinase kinase ? (CaMKK?). In response, AMPK impinges on the autophagy regulators Unc-51-like kinase-1 (ULK1) and c-Jun. AMPK is widely recognized as an mTORC1 antagonist that is activated by starvation. We find that aa acutely activate AMPK concurrently with mTOR. We show that AMPK under aa sufficiency acts to sustain autophagy. This may be required to maintain protein homoeostasis and deliver metabolite intermediates for biosynthetic processes. This model is hosted on BioModels Database and identified by: BIOMD0000000640. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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