BNIP3L/NIX regulates both mitophagy and pexophagy

Lea P. Wilhelm, Juan Zapata-Muñoz, Beatriz Villarejo-Zori, Stephanie Pellegrin, Catarina Martins Freire, Ashley M. Toye, Patricia Boya, Ian G. Ganley (Lead / Corresponding author)

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Abstract

Mitochondria and peroxisomes are closely related metabolic organelles, both in terms of origin and in terms of function. Mitochondria and peroxisomes can also be turned over by autophagy, in processes termed mitophagy and pexophagy, respectively. However, despite their close relationship, it is not known if both organelles are turned over under similar conditions, and if so, how this might be coordinated molecularly. Here, we find that multiple selective autophagy pathways are activated upon iron chelation and show that mitophagy and pexophagy occur in a BNIP3L/NIX-dependent manner. We reveal that the outer mitochondrial membrane-anchored NIX protein, previously described as a mitophagy receptor, also independently localises to peroxisomes and drives pexophagy. We show this process happens in vivo, with mouse tissue that lacks NIX having a higher peroxisomal content. We further show that pexophagy is stimulated under the same physiological conditions that activate mitophagy, including cardiomyocyte and erythrocyte differentiation. Taken together, our work uncovers a dual role for NIX, not only in mitophagy but also in pexophagy, thus illustrating the interconnection between selective autophagy pathways.

Original languageEnglish
Article numbere111115
Number of pages19
JournalEMBO Journal
Early online date10 Oct 2022
DOIs
Publication statusPublished - 10 Oct 2022

Keywords

  • Autophagy
  • mitochondria
  • mitophagy
  • peroxisomes
  • pexophagy
  • autophagy

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