Peroxisomes perform beta-oxidation of branched and very-long chain fatty acids, which leads to the formation of reactive oxygen species (ROS) within the peroxisomal lumen. Peroxisomes are therefore prone to ROS-mediated damages. Here, using light to specifically and acutely induce ROS formation within the peroxisomal lumen, we find that cells individually remove ROS-stressed peroxisomes through ubiquitin-dependent pexophagy. Heat shock protein 70 s mediates the translocation of the ubiquitin E3 ligase Stub1 (STIP1 Homology and U-Box Containing Protein 1) onto oxidatively-stressed peroxisomes to promote their selective ubiquitination and autophagic degradation. Artificially targeting Stub1 to healthy peroxisomes is sufficient to trigger pexophagy, suggesting a key role Stub1 plays in regulating peroxisome quality. We further determine that Stub1 mutants found in Ataxia patients are defective in pexophagy induction. Dysfunctional peroxisomal quality control may therefore contribute to the development of Ataxia.

过氧化物酶体对支链和超长链脂肪酸进行β-氧化，从而导致在过氧化物酶体腔内形成活性氧（ROS）。因此，过氧化物酶体容易受到ROS介导的损害。在这里，我们使用光来特异性和急性地诱导过氧化物酶体腔内的ROS形成，我们发现细胞通过遍在蛋白依赖的exophophyyy单独去除ROS应力过氧化物酶体。热休克蛋白70年代介导泛素E3连接酶Stub1（STIP1同源性和含U-Box的蛋白1）易位到氧化应激过氧化物酶体上，以促进它们的选择性泛素化和自噬降解。人为地将Stub1靶向健康的过氧化物酶体足以触发前列腺炎，这表明Stub1在调节过氧化物酶体质量中起关键作用。我们进一步确定在共济失调患者中发现的Stub1突变体在前列腺炎诱导方面存在缺陷。功能异常的过氧化物酶体质量控制因此可能有助于共济失调的发展。