Display options
Cite
Yazdankhah M, Ghosh S, Shang P, et al. BNIP3L-mediated mitophagy is required for mitochondrial remodeling during the differentiation of optic nerve oligodendrocytes. Autophagy. 2021;17(10):3140-3159doi: 10.1080/15548627.2020.1871204.
Yazdankhah, M., Ghosh, S., Shang, P., Stepicheva, N., Hose, S., Liu, H., Chamling, X., Tian, S., Sullivan, M. L. G., Calderon, M. J., Fitting, C. S., Weiss, J., Jayagopal, A., Handa, J. T., Sahel, J. A., Zigler, J. S., Kinchington, P. R., Zack, D. J., & Sinha, D. (2021). BNIP3L-mediated mitophagy is required for mitochondrial remodeling during the differentiation of optic nerve oligodendrocytes. Autophagy, 17(10), 3140-3159. https://doi.org/10.1080/15548627.2020.1871204
Yazdankhah, Meysam, et al. "BNIP3L-mediated mitophagy is required for mitochondrial remodeling during the differentiation of optic nerve oligodendrocytes." Autophagy vol. 17,10 (2021): 3140-3159. doi: https://doi.org/10.1080/15548627.2020.1871204
Yazdankhah M, Ghosh S, Shang P, Stepicheva N, Hose S, Liu H, Chamling X, Tian S, Sullivan MLG, Calderon MJ, Fitting CS, Weiss J, Jayagopal A, Handa JT, Sahel JA, Zigler JS, Kinchington PR, Zack DJ, Sinha D. BNIP3L-mediated mitophagy is required for mitochondrial remodeling during the differentiation of optic nerve oligodendrocytes. Autophagy. 2021 Oct;17(10):3140-3159. doi: 10.1080/15548627.2020.1871204. Epub 2021 Jan 19. PMID: 33404293; PMCID: PMC8526037.
Copy Download .nbib Format: NLM
Share it on

Autophagy. 2021 Oct;17(10):3140-3159. doi: 10.1080/15548627.2020.1871204. Epub 2021 Jan 19.

BNIP3L-mediated mitophagy is required for mitochondrial remodeling during the differentiation of optic nerve oligodendrocytes.

Autophagy

Meysam Yazdankhah, Sayan Ghosh, Peng Shang, Nadezda Stepicheva, Stacey Hose, Haitao Liu, Xitiz Chamling, Shenghe Tian, Mara L G Sullivan, Michael Joseph Calderon, Christopher S Fitting, Joseph Weiss, Ashwath Jayagopal, James T Handa, José-Alain Sahel, J Samuel Zigler, Paul R Kinchington, Donald J Zack, Debasish Sinha

Affiliations

  1. Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  2. Department of Ophthalmology, Wilmer Eye Institute, the Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  3. Department of Cell Biology and Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  4. Kodiak Sciences, Palo Alto, CA, USA.
  5. Institut De La Vision, INSERM, CNRS, Sorbonne Université, Paris, France.

PMID: 33404293 PMCID: PMC8526037 DOI: 10.1080/15548627.2020.1871204

Abstract

Retinal ganglion cell axons are heavily myelinated (98%) and myelin damage in the optic nerve (ON) severely affects vision. Understanding the molecular mechanism of oligodendrocyte progenitor cell (OPC) differentiation into mature oligodendrocytes will be essential for developing new therapeutic approaches for ON demyelinating diseases. To this end, we developed a new method for isolation and culture of ON-derived oligodendrocyte lineage cells and used it to study OPC differentiation. A critical aspect of cellular differentiation is macroautophagy/autophagy, a catabolic process that allows for cell remodeling by degradation of excess or damaged cellular molecules and organelles. Knockdown of ATG9A and BECN1 (pro-autophagic proteins involved in the early stages of autophagosome formation) led to a significant reduction in proliferation and survival of OPCs. We also found that autophagy flux (a measure of autophagic degradation activity) is significantly increased during progression of oligodendrocyte differentiation. Additionally, we demonstrate a significant change in mitochondrial dynamics during oligodendrocyte differentiation, which is associated with a significant increase in programmed mitophagy (selective autophagic clearance of mitochondria). This process is mediated by the mitophagy receptor BNIP3L (BCL2/adenovirus E1B interacting protein 3-like). BNIP3L-mediated mitophagy plays a crucial role in the regulation of mitochondrial network formation, mitochondrial function and the viability of newly differentiated oligodendrocytes. Our studies provide novel evidence that proper mitochondrial dynamics is required for establishment of functional mitochondria in mature oligodendrocytes. These findings are significant because targeting BNIP3L-mediated programmed mitophagy may provide a novel therapeutic approach for stimulating myelin repair in ON demyelinating diseases.

Keywords: ATG9A; autophagy; autophagy flux; co-culture; demyelinating diseases; glial cells; mitochondrial dynamics; myelin; oligodendrocyte lineage cells; retinal ganglion cell axons

References

  1. EMBO J. 2017 Jun 14;36(12):1688-1706 - PubMed
  2. Nat Rev Mol Cell Biol. 2018 Jan 23;19(2):76 - PubMed
  3. Oxid Med Cell Longev. 2014;2014:210934 - PubMed
  4. Front Oncol. 2017 May 02;7:81 - PubMed
  5. PLoS One. 2014 Sep 23;9(9):e107649 - PubMed
  6. Cell Death Dis. 2014 Sep 04;5:e1403 - PubMed
  7. Nat Rev Immunol. 2019 Mar;19(3):170-183 - PubMed
  8. Mol Cell. 2015 Nov 19;60(4):685-96 - PubMed
  9. Curr Biol. 2018 Feb 19;28(4):R170-R185 - PubMed
  10. Glia. 2016 May;64(5):810-25 - PubMed
  11. Transl Oncol. 2018 Jun;11(3):755-763 - PubMed
  12. Autophagy. 2016;12(2):369-80 - PubMed
  13. Exp Eye Res. 2018 Mar;168:12-18 - PubMed
  14. Autophagy. 2017 Oct 3;13(10):1754-1766 - PubMed
  15. Dev Cell. 2008 Feb;14(2):193-204 - PubMed
  16. Cold Spring Harb Perspect Biol. 2015 Jun 22;8(1):a020479 - PubMed
  17. Genes Dev. 2015 May 15;29(10):989-99 - PubMed
  18. Aging Cell. 2017 Apr;16(2):349-359 - PubMed
  19. Methods Enzymol. 2009;452:181-97 - PubMed
  20. Cell Res. 2012 Feb;22(2):432-5 - PubMed
  21. Cell Transplant. 2019 May;28(5):585-595 - PubMed
  22. J Cell Biol. 1999 Jun 14;145(6):1209-18 - PubMed
  23. Exp Eye Res. 2018 Sep;174:173-184 - PubMed
  24. Cell Res. 2017 Feb;27(2):161-162 - PubMed
  25. J Biol Chem. 2013 Jan 11;288(2):915-26 - PubMed
  26. J Neurosci. 2020 Jan 8;40(2):256-266 - PubMed
  27. Cell Metab. 2018 Feb 6;27(2):439-449.e5 - PubMed
  28. Neurochem Res. 2019 Nov;44(11):2482-2498 - PubMed
  29. Elife. 2016 Nov 17;5: - PubMed
  30. EMBO Mol Med. 2013 Mar;5(3):327-31 - PubMed
  31. PLoS One. 2015 Jan 12;10(1):e0116624 - PubMed
  32. Autophagy. 2019 Sep;15(9):1606-1619 - PubMed
  33. Biochim Biophys Acta. 2015 Oct;1853(10 Pt B):2775-83 - PubMed
  34. Dev Cell. 2004 Apr;6(4):463-77 - PubMed
  35. Development. 2018 Feb 26;145(4): - PubMed
  36. J Ophthalmic Vis Res. 2010 Jul;5(3):182-7 - PubMed
  37. Nat Cell Biol. 2010 Sep;12(9):823-30 - PubMed
  38. Eur J Neurol. 2012 Feb;19(2):241-7 - PubMed
  39. Semin Neurol. 2016 Apr;36(2):185-95 - PubMed
  40. Autophagy. 2019 Jul;15(7):1182-1198 - PubMed
  41. J Cell Biol. 2008 Dec 1;183(5):795-803 - PubMed
  42. Cell Death Differ. 2011 Apr;18(4):571-80 - PubMed
  43. J Neurochem. 2003 Jun;85(6):1500-12 - PubMed
  44. Sci Rep. 2019 Mar 5;9(1):3606 - PubMed
  45. Biochem Biophys Res Commun. 2018 May 27;500(1):59-64 - PubMed
  46. Commun Biol. 2019 Sep 20;2:348 - PubMed
  47. Invest Ophthalmol Vis Sci. 2018 Mar 20;59(4):AMD104-AMD113 - PubMed
  48. Oncogene. 2013 Jul 11;32(28):3311-8 - PubMed
  49. Nat Cell Biol. 2018 Sep;20(9):1013-1022 - PubMed
  50. Glia. 2019 Sep;67(9):1745-1759 - PubMed
  51. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19500-5 - PubMed
  52. Front Cell Neurosci. 2018 Nov 19;12:424 - PubMed
  53. J Biol Chem. 2019 Sep 20;294(38):13852-13863 - PubMed
  54. Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15077-82 - PubMed
  55. J Cell Sci. 2012 Feb 15;125(Pt 4):807-15 - PubMed
  56. Nature. 2019 Jun;570(7761):E34-E42 - PubMed
  57. Sci Rep. 2017 Oct 26;7(1):14133 - PubMed
  58. Autophagy. 2013 Nov 1;9(11):1720-36 - PubMed
  59. Nat Protoc. 2017 Aug;12(8):1576-1587 - PubMed
  60. Mult Scler. 2010 Jul;16(7):786-95 - PubMed
  61. Methods Mol Biol. 2018;1791:95-113 - PubMed
  62. Front Neurol. 2011 Aug 02;2:50 - PubMed
  63. J Vis Exp. 2011 Aug 21;(54): - PubMed
  64. Autophagy. 2020 Jun;16(6):1130-1142 - PubMed
  65. Oncogene. 2013 May 2;32(18):2261-72, 2272e.1-11 - PubMed
  66. Curr Protoc Neurosci. 2001 May;Chapter 3:Unit 3.4 - PubMed
  67. Genes Cells. 2008 Dec;13(12):1249-56 - PubMed
  68. Prog Retin Eye Res. 2021 Mar;81:100886 - PubMed
  69. Nature. 2008 Jul 10;454(7201):232-5 - PubMed
  70. Biochem Biophys Res Commun. 2020 May 14;525(4):954-961 - PubMed
  71. Stem Cells Transl Med. 2017 Nov;6(11):1972-1986 - PubMed
  72. Antioxid Redox Signal. 2011 May 15;14(10):1939-51 - PubMed
  73. J Neurosci. 2016 Oct 12;36(41):10560-10573 - PubMed

Publication Types

Grant support