Spatiotemporal Control of ULK1 Activation by NDP52 and TBK1 during Selective Autophagy

Selective autophagy recycles damaged organelles and clears intracellular pathogens to prevent their aberrant accumulation. How ULK1 kinase is targeted and activated during selective autophagic events remains to be elucidated. In this study, we used chemically inducible dimerization (CID) assays in tandem with CRISPR KO lines to systematically analyze the molecular basis of selective autophagosome biogenesis. We demonstrate that ectopic placement of NDP52 on mitochondria or peroxisomes is sufficient to initiate selective autophagy by focally localizing and activating the ULK1 complex. The capability of NDP52 to induce mitophagy is dependent on its interaction with the FIP200/ULK1 complex, which is facilitated…

• WT
  Wellcome Trust

  Award: WT104752MA
• NI
  National Institutes of Health
• MR
  Medical Research Council

  Award: U105170648
• NI
  National Institute of Neurological Disorders and Stroke