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.

中文翻译：

---

BNIP3L/NIX 调节线粒体自噬和 pexophagy

线粒体和过氧化物酶体是密切相关的代谢细胞器，无论是起源还是功能。线粒体和过氧化物酶体也可以通过自噬进行翻转，过程分别称为线粒体自噬和过氧化物酶体自噬。然而，尽管它们关系密切，但尚不清楚这两个细胞器是否在相似条件下翻转，如果是这样，这可能如何在分子上进行协调。在这里，我们发现多种选择性自噬途径在铁螯合后被激活，并表明线粒体自噬和 pexophagy 以 BNIP3L/NIX 依赖性方式发生。我们揭示了线粒体外膜锚定的 NIX 蛋白，之前被描述为线粒体自噬受体，也独立定位于过氧化物酶体并驱动过氧化物酶体自噬。我们展示了这个过程发生在体内，缺乏 NIX 的小鼠组织具有更高的过氧化物酶体含量。我们进一步表明，在激活线粒体自噬的相同生理条件下会刺激 pexophagy，包括心肌细胞和红细胞分化。综上所述，我们的工作揭示了 NIX 的双重作用，不仅在线粒体自噬中，而且在 pexophagy 中，从而说明了选择性自噬途径之间的相互联系。