Peroxisomes are essential for a number of cellular functions, including reactive oxygen species metabolism, fatty acid β-oxidation and lipid synthesis. To ensure optimal functionality, peroxisomal size, shape and number must be dynamically maintained; however, many aspects of how this is regulated remain poorly characterised. Here, we show that the localisation of Miro1 and Miro2-outer mitochondrial membrane proteins essential for mitochondrial trafficking-to peroxisomes is not required for basal peroxisomal distribution and long-range trafficking, but rather for the maintenance of peroxisomal size and morphology through peroxisomal fission. Mechanistically, this is achieved by Miro negatively regulating Drp1-dependent fission, a function that is shared with the mitochondria. We further find that the peroxisomal localisation of Miro is regulated by its first GTPase domain and is mediated by an interaction through its transmembrane domain with the peroxisomal-membrane protein chaperone, Pex19. Our work highlights a shared regulatory role of Miro in maintaining the morphology of both peroxisomes and mitochondria, supporting a crosstalk between peroxisomal and mitochondrial biology.

中文翻译：

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过氧化物酶体裂变受线粒体 Rho-GTPase、Miro1 和 Miro2 调节。

过氧化物酶体对许多细胞功能至关重要，包括活性氧代谢、脂肪酸 β-氧化和脂质合成。为确保最佳功能，必须动态维持过氧化物酶体的大小、形状和数量；然而，如何监管的许多方面仍然缺乏特征。在这里，我们表明 Miro1 和 Miro2 线粒体外膜蛋白的定位对于线粒体运输到过氧化物酶体至关重要，这对于基础过氧化物酶体分布和远程运输不是必需的，而是通过过氧化物酶体裂变维持过氧化物酶体的大小和形态。从机制上讲，这是通过 Miro 负调节 Drp1 依赖性裂变来实现的，这是一种与线粒体共享的功能。我们进一步发现 Miro 的过氧化物酶体定位受其第一个 GTPase 结构域的调节，并通过其跨膜结构域与过氧化物酶体膜蛋白伴侣 Pex19 的相互作用介导。我们的工作强调了 Miro 在维持过氧化物酶体和线粒体形态方面的共同调节作用，支持过氧化物酶体和线粒体生物学之间的串扰。