Vps35 Mediates Vesicle Transport between the Mitochondria and Peroxisomes
Vps35 Mediates Vesicle Transport between the Mitochondria and Peroxisomes
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DOI：
10.1016/j.cub.2010.05.066
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发表时间：
2010-07-27
期刊：
影响因子：
9.2
通讯作者：
McBride, Heidi M.
中科院分区：
文献类型：
--
作者：
Braschi, Emelie;Goyon, Vanessa;McBride, Heidi M.
线粒体衍生的囊泡（MDV）已被证明可以将货物从线粒体转运到过氧化物酶体[1]。线粒体和过氧化物酶体在氧化脂肪酸和减少破坏性过氧化物方面具有共同的功能[2，3]。它们的生物发生也通过激活主转录因子如PGC-1 α [4，5]和常见的裂变机制，包括DRP 1，Mff和hFis 1 [6-9]。我们先前已经证明MDV是独立于已知线粒体形成的！裂殖GTdR Drp 1，并富含线粒体小泛素样修饰物（SUMO）E3连接酶，称为MAPL（线粒体锚定蛋白连接酶）[1]。在这里，我们证明了逆转录酶复合物，一种已知的囊泡从内体转运到高尔基体的组分[10-13]，调节MAPL从线粒体到过氧化物酶体的转运。无偏筛选显示Vps 35和Vps 26与MAPL复合，共聚焦成像显示Vps 35募集到线粒体！囊泡Vps 35或Vps 26 A的沉默导致MAPL向过氧化物酶体的递送显著减少，将逆转录聚合物置于新的细胞内运输途径内，并提供对MAPL阳性MDV形成的深入了解。
Mitochondria-derived vesicles (MDVs) have been shown to transport cargo from the mitochondria to the peroxisomes [1]. Mitochondria and peroxisomes share common functions in the oxidation of fatty acids and the reduction of damaging peroxides [2, 3]. Their biogenesis is also linked through both the activation of master transcription factors such as PGC-1 alpha [4, 5] and the common use of fission machinery, including DRP1, Mff, and hFis1 [6-9]. We have previously shown that MDVs are formed independently of the known mitochondria! fission GTPase Drp1 and are enriched for a mitochondrial small ubiquitin-like modifier (SUMO) E3 ligase called MAPL (mitochondrial-anchored protein ligase) [1]. Here, we demonstrate that the retromer complex, a known component of vesicle transport from the endosome to the Golgi apparatus [10-13], regulates the transport of MAPL from mitochondria to peroxisomes. An unbiased screen shows that Vps35 and Vps26 are found in complex with MAPL, and confocal imaging reveals Vps35 recruitment to mitochondria! vesicles. Silencing of Vps35 or Vps26A leads to a significant reduction in the delivery of MAPL to peroxisomes, placing the retromer within a novel intracellular trafficking route and providing insight into the formation of MAPL-positive MDVs.