FKBP5/FKBP51 enhances autophagy to synergize with antidepressant action

Autophagy. 2015;11(3):578-80. doi: 10.1080/15548627.2015.1017224.

Abstract

Levels of autophagy markers rise upon treatment of cells with antidepressants. However, it was not known whether this phenomenon might be linked to other antidepressant pathways or to any physiological effect. In this punctum, we summarize and discuss our recent findings that provide evidence for a role of the cochaperone FKBP5/FKBP51 (FK506 binding protein 5) in autophagy as a prerequisite for antidepressant action in cells, mice, and humans. FKBP5 associates with BECN1, changes its phosphorylation and protein levels and enhances markers of autophagy and autophagic flux. The effects of antidepressants on autophagy as well as their physiological effects in mice and human depend on FKBP5.

Keywords: Beclin 1; FKBP5; FKBP51; antidepressant; autophagy; depression.

MeSH terms

  • Amitriptyline / chemistry
  • Animals
  • Antidepressive Agents / chemistry*
  • Apoptosis Regulatory Proteins / metabolism*
  • Autophagy*
  • Beclin-1
  • Behavior, Animal
  • Depression / drug therapy
  • Electrophysiology
  • Gene Expression Regulation
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Immunoprecipitation
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Chaperones / metabolism
  • Paroxetine / chemistry
  • Phosphorylation
  • Tacrolimus Binding Proteins / metabolism*

Substances

  • Antidepressive Agents
  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Becn1 protein, mouse
  • HSP90 Heat-Shock Proteins
  • Membrane Proteins
  • Molecular Chaperones
  • Amitriptyline
  • Paroxetine
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5