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Updated: Jun 24, 2025

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates
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Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Published on: February 27, 2016

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Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation status

Patricia Marqués1, Jesús Burillo2, Carlos González-Blanco1,2,3,4

  • 1Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University of Madrid, Madrid, Spain.

Scientific Reports
|May 31, 2024
PubMed

Insights

Sirtuin1 (SIRT1) activation by resveratrol deacetylates tuberous sclerosis complex 2 (TSC2), inhibiting mTORC1 signaling and enhancing autophagy. This improves mitochondrial quality control, crucial for pancreatic beta cell homeostasis and preventing Type 2 Diabetes Mellitus.

Area of Science:

  • Cellular Biology
  • Metabolic Research
  • Molecular Mechanisms

Background:

  • Sirtuin1 (SIRT1) deacetylates tuberous sclerosis complex 2 (TSC2), impacting mTORC1 signaling and autophagy.
  • TSC2 acetylation influences its lysosomal translocation and mitochondrial turnover.

Purpose of the Study:

  • To investigate the role of TSC2 acetylation in lysosomal translocation and mitochondrial turnover.
  • To analyze the effects of SIRT1 activation on TSC2 acetylation and cellular processes.

Main Methods:

  • Utilized mouse embryonic fibroblast (MEF) and MIN6 cells (pancreatic beta cell model).
  • Administered resveratrol (RESV) to activate SIRT1.
  • Assessed TSC2 acetylation, mTORC1 signaling, autophagy, and mitochondrial dynamics.

Main Results:

  • Resveratrol promoted TSC2 deacetylation and lysosomal translocation, inhibiting mTORC1.
  • RESV treatment enhanced mitochondrial turnover, increased fissioned mitochondria, and boosted autophagic/mitophagic fluxes.
  • Mitochondrial biogenesis was also enhanced.

Conclusions:

  • Deacetylated TSC2 is essential for regulating mTORC1 signaling and maintaining mitochondrial quality control.
  • This process is vital for pancreatic beta cell homeostasis and preventing metabolic disorders like Type 2 Diabetes Mellitus.
Keywords:
AcetylationLysosomeMitophagyPancreatic β cellsTSC2mTORC1

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