08 Apr 2020 - TBK1-mediated phosphorylation of LC3C and GABARAP-L2 controls autophagosome shedding by ATG4 protease

Here we present a new regulatory mechanism of autophagy, which influences the conjugation and de-conjugation of autophagy modifiers to autophagosomes. TBK1 phosphorylates LC3C and GABARAP-L2, which impedes LC3 binding to the processing enzyme ATG4.


  • TBK1 phosphorylates autophagy modifiers LC3C and GABARAP-L2 on surface-exposed serine-residues.
  • GABARAP-L2 S87/88-PO4 and LC3C S93/96-PO4 impedes binding to the ATG4 protease.
  • Phosphorylated LC3C/GABARAP-L2 are protected from ATG4-mediated premature removal from autophagosomes.