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Study of Protein-protein Interactions in Autophagy Research
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Folliculin regulates ampk-dependent autophagy and metabolic stress survival

Elite Possik1, Zahra Jalali1, Yann Nouët1

  • 1Goodman Cancer Research Center, McGill University, Montréal, Québec, Canada; Department of Biochemistry, McGill University, Montréal, Québec, Canada.

Plos Genetics
|April 26, 2014
PubMed

Insights

Folliculin (FLCN) negatively regulates AMP-activated protein kinase (AMPK). Loss of FLCN causes constitutive AMPK activation, promoting cell survival and stress resistance, suggesting FLCN’s tumor suppressor role.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Genetics

Background:

  • AMP-activated protein kinase (AMPK) signaling is crucial in human diseases.
  • Dysregulated AMPK is linked to various pathologies, highlighting the need to understand its regulators.
  • The tumor suppressor Folliculin (FLCN), linked to Birt-Hogg Dubé syndrome, interacts with AMPK, but their functional relationship is unclear.

Purpose of the Study:

  • To investigate the genetic and functional links between Folliculin (FLCN) and AMP-activated protein kinase (AMPK).
  • To determine the role of FLCN in regulating AMPK signaling and its implications in cellular processes and disease.
  • To establish FLCN as a tumor suppressor by elucidating its mechanism involving AMPK.

Main Methods:

  • Utilized Caenorhabditis elegans and mammalian cell models.
  • Investigated the effects of FLCN loss on AMPK activity and downstream cellular responses.
  • Assessed cellular bioenergetics, apoptosis, autophagy, and stress resistance under various conditions.

Main Results:

  • Folliculin (FLCN) acts as an evolutionarily conserved negative regulator of AMPK.
  • Loss of FLCN leads to constitutive AMPK activation, independent of cellular energy status.
  • FLCN-deficient cells exhibit enhanced autophagy, inhibited apoptosis, improved bioenergetics, and increased resistance to diverse stresses.

Conclusions:

  • FLCN is a critical regulator of AMPK energy sensing and signaling.
  • FLCN may function as a tumor suppressor by inhibiting AMPK.
  • Understanding the FLCN-AMPK axis provides insights into Birt-Hogg Dubé syndrome pathogenesis and potential therapeutic strategies.

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