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Shen JL, Fortier TM, Zhao YG, et al. Vmp1, Vps13D, and Marf/Mfn2 function in a conserved pathway to regulate mitochondria and ER contact in development and disease. Curr Biol. 2021;31(14):3028-3039.e7doi: 10.1016/j.cub.2021.04.062.
Shen, J. L., Fortier, T. M., Zhao, Y. G., Wang, R., Burmeister, M., & Baehrecke, E. H. (2021). Vmp1, Vps13D, and Marf/Mfn2 function in a conserved pathway to regulate mitochondria and ER contact in development and disease. Current biology : CB, 31(14), 3028-3039.e7. https://doi.org/10.1016/j.cub.2021.04.062
Shen, James L, et al. "Vmp1, Vps13D, and Marf/Mfn2 function in a conserved pathway to regulate mitochondria and ER contact in development and disease." Current biology : CB vol. 31,14 (2021): 3028-3039.e7. doi: https://doi.org/10.1016/j.cub.2021.04.062
Shen JL, Fortier TM, Zhao YG, Wang R, Burmeister M, Baehrecke EH. Vmp1, Vps13D, and Marf/Mfn2 function in a conserved pathway to regulate mitochondria and ER contact in development and disease. Curr Biol. 2021 Jul 26;31(14):3028-3039.e7. doi: 10.1016/j.cub.2021.04.062. Epub 2021 May 20. PMID: 34019822; PMCID: PMC8319081.
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Curr Biol. 2021 Jul 26;31(14):3028-3039.e7. doi: 10.1016/j.cub.2021.04.062. Epub 2021 May 20.

Vmp1, Vps13D, and Marf/Mfn2 function in a conserved pathway to regulate mitochondria and ER contact in development and disease.

Current biology : CB

James L Shen, Tina M Fortier, Yan G Zhao, Ruoxi Wang, Margit Burmeister, Eric H Baehrecke

Affiliations

  1. Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  2. Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
  3. Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: [email protected].

PMID: 34019822 PMCID: PMC8319081 DOI: 10.1016/j.cub.2021.04.062

Abstract

Mutations in Vps13D cause defects in autophagy, clearance of mitochondria, and human movement disorders. Here, we discover that Vps13D functions in a pathway downstream of Vmp1 and upstream of Marf/Mfn2. Like vps13d, vmp1 mutant cells exhibit defects in autophagy, mitochondrial size, and clearance. Through the relationship between vmp1 and vps13d, we reveal a novel role for Vps13D in the regulation of mitochondria and endoplasmic reticulum (ER) contact. Significantly, the function of Vps13D in mitochondria and ER contact is conserved between fly and human cells, including fibroblasts derived from patients suffering from VPS13D mutation-associated neurological symptoms. vps13d mutants have increased levels of Marf/MFN2, a regulator of mitochondrial fusion. Importantly, loss of marf/MFN2 suppresses vps13d mutant phenotypes, including mitochondria and ER contact. These findings indicate that Vps13d functions at a regulatory point between mitochondria and ER contact, mitochondrial fusion and autophagy, and help to explain how Vps13D contributes to disease.

Copyright © 2021 Elsevier Inc. All rights reserved.

Keywords: Drosophila; Vmp1; Vps13D; autophagy; membrane contact; mitochondria

Conflict of interest statement

Declaration of interests E.H.B. is a member of the Advisory Board of Current Biology. All other authors declare no competing interests.

References

  1. Cell Death Differ. 2012 Aug;19(8):1299-307 - PubMed
  2. Curr Biol. 2018 Jan 22;28(2):287-295.e6 - PubMed
  3. J Cell Biol. 2018 Jan 2;217(1):251-268 - PubMed
  4. J Cell Biol. 2018 Oct 1;217(10):3625-3639 - PubMed
  5. EMBO Rep. 2017 Nov;18(11):1893-1904 - PubMed
  6. J Cell Biol. 2018 Oct 1;217(10):3322-3324 - PubMed
  7. Dev Cell. 2014 Feb 24;28(4):450-8 - PubMed
  8. PLoS Biol. 2010 Jan 26;8(1):e1000298 - PubMed
  9. J Innate Immun. 2015;7(5):545-53 - PubMed
  10. Science. 2011 Oct 21;334(6054):358-62 - PubMed
  11. Cell Metab. 2020 Sep 1;32(3):479-497.e9 - PubMed
  12. Nat Cell Biol. 2013 Sep;15(9):1067-78 - PubMed
  13. Mol Cell Neurosci. 2013 Jul;55:26-36 - PubMed
  14. Nature. 2008 Dec 4;456(7222):605-10 - PubMed
  15. Cell. 2010 May 14;141(4):656-67 - PubMed
  16. Trends Neurosci. 2016 Mar;39(3):146-157 - PubMed
  17. Cell Metab. 2018 Feb 6;27(2):439-449.e5 - PubMed
  18. CNS Neurosci Ther. 2019 Jul;25(7):859-875 - PubMed
  19. Genetics. 2005 Feb;169(2):737-50 - PubMed
  20. Elife. 2019 Feb 11;8: - PubMed
  21. Science. 2015 Nov 27;350(6264):1092-6 - PubMed
  22. Science. 2015 Nov 27;350(6264):1096-101 - PubMed
  23. Neuromolecular Med. 2006;8(1-2):43-62 - PubMed
  24. Genesis. 2002 Sep-Oct;34(1-2):58-61 - PubMed
  25. Ann Neurol. 2018 Jun;83(6):1089-1095 - PubMed
  26. Genomics. 2004 Sep;84(3):536-49 - PubMed
  27. Dev Biol. 2002 Oct 1;250(1):101-11 - PubMed
  28. Nat Cell Biol. 2018 Sep;20(9):1013-1022 - PubMed
  29. J Cell Biol. 2017 Oct 2;216(10):3219-3229 - PubMed
  30. Antioxid Redox Signal. 2015 Apr 20;22(12):995-1019 - PubMed
  31. Nature. 2013 Mar 21;495(7441):389-93 - PubMed
  32. Elife. 2018 Apr 20;7: - PubMed
  33. Development. 1997 Nov;124(22):4673-83 - PubMed
  34. Genetics. 2014 Apr;196(4):961-71 - PubMed
  35. Ann Oncol. 2016 Apr;27(4):738-44 - PubMed
  36. Proc Natl Acad Sci U S A. 2016 Oct 4;113(40):11249-11254 - PubMed
  37. Elife. 2017 Apr 25;6: - PubMed
  38. Sci Transl Med. 2010 Aug 4;2(43):43ra55 - PubMed
  39. J Cell Biol. 1997 Oct 6;139(1):23-36 - PubMed
  40. PLoS One. 2012;7(8):e44214 - PubMed
  41. J Cell Biol. 2018 May 7;217(5):1613-1622 - PubMed
  42. Nat Genet. 2017 Dec;49(12):1779-1784 - PubMed
  43. Ann Neurol. 2018 Jun;83(6):1075-1088 - PubMed
  44. Cell. 2010 Jun 11;141(6):1042-55 - PubMed
  45. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5018-23 - PubMed
  46. Mol Cell. 2017 Sep 21;67(6):974-989.e6 - PubMed

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