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

• DOI: 10.1016/j.molcel.2019.02.010
• Publication Date: 2019-03-07T15:56:16Z
• Authors: Jose Norberto S. ...; Chunxin Wang; Eric Bunker; Ling Hao; Dragan Maric; Giampietro Schiavo; Felix Randow; Richard J. Youle
• Keywords: ULK1

Highlights•NDP52 associates with the ULK1 complex through FIP200, facilitated by TBK1•NDP52/TBK1 targets to cargo initiate autophagy in absence of LC3•ULK1 is activated on independently AMPK and mTOR activity•Ectopic recruitment FIP200-binding peptide sufficient degrade cargoSummarySelective recycles damaged organelles clears intracellular pathogens prevent their aberrant accumulation. How kinase targeted during selective autophagic events remains be elucidated. In this study, we used chemically inducible dimerization (CID) assays tandem CRISPR KO lines systematically analyze molecular basis autophagosome biogenesis. We demonstrate that ectopic placement NDP52 mitochondria or peroxisomes focally localizing activating complex. The capability induce mitophagy dependent its interaction FIP200/ULK1 complex, which TBK1. Ectopically tethering bypasses requirement for receptors Focal activation occurs mTOR. Our findings provide a parsimonious model autophagy, highlights coordination localization TBK1 as principal drivers biogenesis.Graphical abstract