Peroxisomal protein PEX13 functions in selective autophagy

Ming Y. Lee, Rhea Sumpter, Zhongju Zou, Shyam Sirasanagandla, Yongjie Wei, Prashant Mishra, Hendrik Rosewich, Denis I. Crane, Beth Levine

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

PEX13 is an integral membrane protein on the peroxisome that regulates peroxisomal matrix protein import during peroxisome biogenesis. Mutations in PEX13 and other peroxin proteins are associated with Zellweger syndrome spectrum (ZSS) disorders, a subtype of peroxisome biogenesis disorder characterized by prominent neurological, hepatic, and renal abnormalities leading to neonatal death. The lack of functional peroxisomes in ZSS patients is widely accepted as the underlying cause of disease; however, our understanding of disease pathogenesis is still incomplete. Here, we demonstrate that PEX13 is required for selective autophagy of Sindbis virus (virophagy) and of damaged mitochondria (mitophagy) and that disease-associated PEX13 mutants I326T and W313G are defective in mitophagy. The mitophagy function of PEX13 is shared with another peroxin family member PEX3, but not with two other peroxins, PEX14 and PEX19, which are required for general autophagy. Together, our results demonstrate that PEX13 is required for selective autophagy, and suggest that dysregulation of PEX13-mediated mitophagy may contribute to ZSS pathogenesis.

Original languageEnglish (US)
Pages (from-to)48-60
Number of pages13
JournalEMBO Reports
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2017

Keywords

  • PEX13
  • Zellweger syndrome
  • autophagy
  • mitophagy
  • virophagy

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Lee, M. Y., Sumpter, R., Zou, Z., Sirasanagandla, S., Wei, Y., Mishra, P., Rosewich, H., Crane, D. I., & Levine, B. (2017). Peroxisomal protein PEX13 functions in selective autophagy. EMBO Reports, 18(1), 48-60. https://doi.org/10.15252/embr.201642443