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Poole LP, Bock-Hughes A, Berardi DE, et al. ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3. Sci Rep. 2021;11(1):20526doi: 10.1038/s41598-021-00170-4.
Poole, L. P., Bock-Hughes, A., Berardi, D. E., & Macleod, K. F. (2021). ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3. Scientific reports, 11(1), 20526. https://doi.org/10.1038/s41598-021-00170-4
Poole, Logan P, et al. "ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3." Scientific reports vol. 11,1 (2021): 20526. doi: https://doi.org/10.1038/s41598-021-00170-4
Poole LP, Bock-Hughes A, Berardi DE, Macleod KF. ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3. Sci Rep. 2021 Oct 15;11(1):20526. doi: 10.1038/s41598-021-00170-4. PMID: 34654847; PMCID: PMC8519931.
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Sci Rep. 2021 Oct 15;11(1):20526. doi: 10.1038/s41598-021-00170-4.

ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3.

Scientific reports

Logan P Poole, Althea Bock-Hughes, Damian E Berardi, Kay F Macleod

Affiliations

  1. The Ben May Department for Cancer Research, The University of Chicago, Chicago, USA.
  2. The Committee on Cancer Biology, The University of Chicago, Chicago, USA.
  3. The Committee on Molecular Metabolism and Nutrition, The University of Chicago, Chicago, USA.
  4. The Ben May Department for Cancer Research, The University of Chicago, Chicago, USA. [email protected].
  5. The Committee on Cancer Biology, The University of Chicago, Chicago, USA. [email protected].
  6. The Committee on Molecular Metabolism and Nutrition, The University of Chicago, Chicago, USA. [email protected].

PMID: 34654847 PMCID: PMC8519931 DOI: 10.1038/s41598-021-00170-4

Abstract

UNC51-like kinase-1 (ULK1) is the catalytic component of the autophagy pre-initiation complex that stimulates autophagy via phosphorylation of ATG14, BECLN1 and other autophagy proteins. ULK1 has also been shown to specifically promote mitophagy but the mechanistic basis of how has remained unclear. Here we show that ULK1 phosphorylates the BNIP3 mitochondrial cargo receptor on a critical serine residue (S17) adjacent to its amino terminal LIR motif. ULK1 similarly phosphorylates BNIP3L on S35. Phosphorylation of BNIP3 on S17 by ULK1 promotes interaction with LC3 and mitophagy. ULK1 interaction also promotes BNIP3 protein stability by limiting its turnover at the proteasome. The ability of ULK1 to regulate BNIP3 protein stability depends on an intact "BH3" domain and deletion of its "BH3" domain reduces BNIP3 turnover and increases BNIP3 protein levels independent of ULK1. In summary ULK1 promotes mitophagy by both stabilization of BNIP3 protein and via phosphorylation of S17 to stimulate interaction with LC3.

© 2021. The Author(s).

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