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Upregulated pexophagy limits the capacity of selective autophagy

Author

Listed:
  • Kyla Germain

    (The Hospital for Sick Children
    University of Toronto)

  • Raphaella W. L. So

    (University of Toronto
    Tanz Centre for Research in Neurodegenerative Diseases)

  • Laura F. DiGiovanni

    (The Hospital for Sick Children
    University of Toronto)

  • Joel C. Watts

    (University of Toronto
    Tanz Centre for Research in Neurodegenerative Diseases)

  • Robert H. J. Bandsma

    (The Hospital for Sick Children
    University of Toronto)

  • Peter K. Kim

    (The Hospital for Sick Children
    University of Toronto)

Abstract

Selective autophagy is an essential process to maintain cellular homeostasis through the constant recycling of damaged or superfluous components. Over a dozen selective autophagy pathways mediate the degradation of diverse cellular substrates, but whether these pathways can influence one another remains unknown. We address this question using pexophagy, the autophagic degradation of peroxisomes, as a model. We show in cells that upregulated pexophagy impairs the selective autophagy of both mitochondria and protein aggregates by exhausting the autophagy initiation factor, ULK1. We confirm this finding in cell models of the pexophagy-mediated form of Zellweger Spectrum Disorder, a disease characterized by peroxisome dysfunction. Further, we extend the generalizability of limited selective autophagy by determining that increased protein aggregate degradation reciprocally reduces pexophagy using cell models of Parkinson’s Disease and Huntington’s Disease. Our findings suggest that the degradative capacity of selective autophagy can become limited by an increase in one substrate.

Suggested Citation

  • Kyla Germain & Raphaella W. L. So & Laura F. DiGiovanni & Joel C. Watts & Robert H. J. Bandsma & Peter K. Kim, 2024. "Upregulated pexophagy limits the capacity of selective autophagy," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44005-4
    DOI: 10.1038/s41467-023-44005-4
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    References listed on IDEAS

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    1. Michael Lazarou & Danielle A. Sliter & Lesley A. Kane & Shireen A. Sarraf & Chunxin Wang & Jonathon L. Burman & Dionisia P. Sideris & Adam I. Fogel & Richard J. Youle, 2015. "The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy," Nature, Nature, vol. 524(7565), pages 309-314, August.
    2. Bo-Hua Chen & Yao-Jen Chang & Steven Lin & Wei Yuan Yang, 2020. "Hsc70/Stub1 promotes the removal of individual oxidatively stressed peroxisomes," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
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