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Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
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Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions

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Post-translational regulation of mTOR complex 1 in hypoxia and reoxygenation

Chia Yee Tan1, Thilo Hagen

  • 1Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, 117597 Singapore.

Cellular Signalling
|February 19, 2013
PubMed

Insights

Hypoxia rapidly impacts mechanistic target of rapamycin complex 1 (mTORC1) activity. This regulation occurs post-translationally, independent of transcription factors like HIF, suggesting direct mTORC1 modulation.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Physiology

Background:

  • Mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and proliferation.
  • Hypoxia (low oxygen) is known to inhibit mTORC1 activity through various proposed transcriptional mechanisms.
  • Understanding the precise regulation of mTORC1 by oxygen is crucial for cellular homeostasis.

Purpose of the Study:

  • To investigate the dynamic regulation of mTORC1 activity by oxygen concentrations.
  • To elucidate the mechanisms underlying the rapid response of mTORC1 to hypoxia and reoxygenation.
  • To determine if transcriptional or post-translational pathways mediate hypoxia's effect on mTORC1.

Main Methods:

  • Dynamic monitoring of mTORC1 activity under varying oxygen levels.
  • Assessment of the role of HIF transcription factors and their targets (REDD1, BNIP3).
  • Evaluation of the necessity for transcription and new protein synthesis in mTORC1 response.

Main Results:

  • mTORC1 activity responds dynamically and rapidly to changes in oxygen concentration.
  • The rapid response is independent of HIF transcription factors and their downstream targets.
  • Hypoxia-induced mTORC1 regulation occurs post-translationally, bypassing TSC1/2 and Ragulator pathways, suggesting direct mTORC1 interaction.

Conclusions:

  • mTORC1 activity is rapidly modulated by oxygen levels through a post-translational mechanism.
  • This rapid response is independent of transcriptional regulation, including HIF signaling.
  • The findings suggest a direct, potentially heme-protein-mediated, regulation of mTORC1 by oxygen concentration.

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