Display options
Cite
Springer MZ, Poole LP, Drake LE, et al. BNIP3-dependent mitophagy promotes cytosolic localization of LC3B and metabolic homeostasis in the liver. Autophagy. 2021;17(11):3530-3546doi: 10.1080/15548627.2021.1877469.
Springer, M. Z., Poole, L. P., Drake, L. E., Bock-Hughes, A., Boland, M. L., Smith, A. G., Hart, J., Chourasia, A. H., Liu, I., Bozek, G., & Macleod, K. F. (2021). BNIP3-dependent mitophagy promotes cytosolic localization of LC3B and metabolic homeostasis in the liver. Autophagy, 17(11), 3530-3546. https://doi.org/10.1080/15548627.2021.1877469
Springer, Maya Z, et al. "BNIP3-dependent mitophagy promotes cytosolic localization of LC3B and metabolic homeostasis in the liver." Autophagy vol. 17,11 (2021): 3530-3546. doi: https://doi.org/10.1080/15548627.2021.1877469
Springer MZ, Poole LP, Drake LE, Bock-Hughes A, Boland ML, Smith AG, Hart J, Chourasia AH, Liu I, Bozek G, Macleod KF. BNIP3-dependent mitophagy promotes cytosolic localization of LC3B and metabolic homeostasis in the liver. Autophagy. 2021 Nov;17(11):3530-3546. doi: 10.1080/15548627.2021.1877469. Epub 2021 Feb 08. PMID: 33459136; PMCID: PMC8632322.
Copy Download .nbib Format: NLM
Share it on

Autophagy. 2021 Nov;17(11):3530-3546. doi: 10.1080/15548627.2021.1877469. Epub 2021 Feb 08.

BNIP3-dependent mitophagy promotes cytosolic localization of LC3B and metabolic homeostasis in the liver.

Autophagy

Maya Z Springer, Logan P Poole, Lauren E Drake, Althea Bock-Hughes, Michelle L Boland, Alexandra G Smith, John Hart, Aparajita H Chourasia, Ivan Liu, Grazyna Bozek, Kay F Macleod

Affiliations

  1. The Ben May Department for Cancer Research, The Gordon Center for Integrative Sciences, W-338 the University of Chicago, Chicago, IL, USA.
  2. The Committee on Cancer Biology, The University of Chicago, Chicago, IL, USA.
  3. The University of Chicago, Chicago, IL, USA.
  4. Department of Pathology, University of Chicago, Chicago, USA.

PMID: 33459136 PMCID: PMC8632322 DOI: 10.1080/15548627.2021.1877469

Abstract

Mitophagy formed the basis of the original description of autophagy by Christian de Duve when he demonstrated that GCG (glucagon) induced macroautophagic/autophagic turnover of mitochondria in the liver. However, the molecular basis of liver-specific activation of mitophagy by GCG, or its significance for metabolic stress responses in the liver is not understood. Here we show that BNIP3 is required for GCG-induced mitophagy in the liver through interaction with processed LC3B; an interaction that is also necessary to localize LC3B out of the nucleus to cytosolic mitophagosomes in response to nutrient deprivation. Loss of BNIP3-dependent mitophagy caused excess mitochondria to accumulate in the liver, disrupting metabolic zonation within the liver parenchyma, with expansion of zone 1 metabolism at the expense of zone 3 metabolism. These results identify BNIP3 as a regulator of metabolic homeostasis in the liver through its effect on mitophagy and mitochondrial mass distribution.

Keywords: BNIP3; LC3B; glucagon; hepatocyte; liver zonation; mitophagy; nutrient deprivation

References

  1. Dev Cell. 2006 Jun;10(6):759-70 - PubMed
  2. Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6794-9 - PubMed
  3. Mol Cell. 2010 Oct 22;40(2):280-93 - PubMed
  4. EMBO J. 2005 Nov 16;24(22):3846-58 - PubMed
  5. Mol Cell. 2015 Feb 5;57(3):456-66 - PubMed
  6. EMBO Rep. 2017 Jun;18(6):947-961 - PubMed
  7. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19500-5 - PubMed
  8. Mol Cell. 2015 Nov 19;60(4):685-96 - PubMed
  9. Annu Rev Nutr. 1996;16:179-203 - PubMed
  10. Chem Biol. 2011 Aug 26;18(8):1042-52 - PubMed
  11. Mol Cell Biol. 2012 Jul;32(13):2570-84 - PubMed
  12. Redox Biol. 2017 Apr;11:622-630 - PubMed
  13. J Cell Biol. 1967 Nov;35(2):C11-6 - PubMed
  14. Int J Obes (Lond). 2005 Mar;29 Suppl 1:S5-9 - PubMed
  15. J Clin Invest. 2007 Oct;117(10):2825-33 - PubMed
  16. Nat Commun. 2015 Jul 06;6:7527 - PubMed
  17. FEBS Lett. 2019 Feb;593(4):414-422 - PubMed
  18. Am J Physiol Gastrointest Liver Physiol. 2009 Mar;296(3):G499-509 - PubMed
  19. J Cell Biol. 1967 May;33(2):437-49 - PubMed
  20. Nature. 2014 Dec 4;516(7529):112-5 - PubMed
  21. J Biol Chem. 2012 Jun 1;287(23):19094-104 - PubMed
  22. Cell Metab. 2011 Jul 6;14(1):9-19 - PubMed
  23. FEBS Lett. 2008 Jan 9;582(1):46-53 - PubMed
  24. J Clin Invest. 2007 Sep;117(9):2713-22 - PubMed
  25. Nat Cell Biol. 2012 Jan 22;14(2):177-85 - PubMed
  26. Cell Death Differ. 2015 Sep;22(9):1399-401 - PubMed
  27. Redox Biol. 2019 Apr;22:101148 - PubMed
  28. Nature. 2017 Feb 16;542(7641):352-356 - PubMed
  29. EMBO J. 1996 Nov 15;15(22):6178-88 - PubMed
  30. Nat Cell Biol. 2018 Sep;20(9):1013-1022 - PubMed
  31. Annu Rev Physiol. 2015;77:179-200 - PubMed
  32. EMBO Rep. 2010 Jan;11(1):45-51 - PubMed
  33. Mol Biol Cell. 2004 Mar;15(3):1101-11 - PubMed
  34. Nat Rev Cancer. 2018 Oct;18(10):634-645 - PubMed
  35. Int J Mol Sci. 2019 May 11;20(9): - PubMed
  36. Nat Rev Gastroenterol Hepatol. 2019 Jul;16(7):395-410 - PubMed
  37. Nature. 2008 Jul 10;454(7201):232-5 - PubMed

Publication Types

Grant support