OPA1-anchored PKA phosphorylates perilipin 1 on S522 and S497 in adipocytes differentiated from human adipose stem cells

Mol Biol Cell. 2018 Jun 15;29(12):1487-1501. doi: 10.1091/mbc.E17-09-0538. Epub 2018 Apr 24.


Optic atrophy 1 (OPA1) is the A-kinase anchoring protein targeting the pool of protein kinase A (PKA) responsible for perilipin 1 phosphorylation, a gatekeeper for lipolysis. However, the involvement of OPA1-bound PKA in the downstream regulation of lipolysis is unknown. Here we show up-regulation and relocation of OPA1 from mitochondria to lipid droplets during adipocytic differentiation of human adipose stem cells. We employed various biochemical and immunological approaches to demonstrate that OPA1-bound PKA phosphorylates perilipin 1 at S522 and S497 on lipolytic stimulation. We show that the first 30 amino acids of OPA1 are essential for its lipid droplet localization as is OMA1-dependent processing. Finally, our results indicate that presence of OPA1 is necessary for lipolytic phosphorylation of downstream targets. Our results show for the first time, to our knowledge, how OPA1 mediates adrenergic control of lipolysis in human adipocytes by regulating phosphorylation of perilipin 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / metabolism
  • Adipose Tissue / cytology*
  • Biomarkers / metabolism
  • Cell Differentiation*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • GTP Phosphohydrolases / chemistry
  • GTP Phosphohydrolases / metabolism*
  • Humans
  • Lipid Droplets / metabolism
  • Lipolysis
  • Metalloendopeptidases / metabolism
  • Mitochondria / metabolism
  • Perilipin-1 / metabolism*
  • Phosphorylation
  • Phosphoserine / metabolism*
  • Stem Cells / metabolism*
  • Sterol Esterase / metabolism
  • Structure-Activity Relationship
  • Up-Regulation


  • Biomarkers
  • Perilipin-1
  • Phosphoserine
  • Cyclic AMP-Dependent Protein Kinases
  • Sterol Esterase
  • Metalloendopeptidases
  • molecule metalloprotease-related protein-1, human
  • GTP Phosphohydrolases
  • OPA1 protein, human