Rab32 uses its effector reticulon 3L to trigger autophagic degradation of mitochondria-associated membrane (MAM) proteins.
Rab32 uses its effector reticulon 3L to trigger autophagic degradation of mitochondria-associated membrane (MAM) proteins.
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DOI：
10.1186/s13062-021-00311-9
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发表时间：
2021-11-07
期刊：
影响因子：
5.5
通讯作者：
Simmen T
中科院分区：
文献类型：
--
作者：
Herrera-Cruz MS;Yap MC;Tahbaz N;Phillips K;Thomas L;Thomas G;Simmen T
Rab 32是一种与多种细胞器相关的小GTP酶，但在内质网（ER）中特别富集。在这里，它控制靶向ERA-ER接触（MERC），从而影响ERA-associated membrane（MAM）的组成。此外，Rab 32通过其效应动力蛋白相关蛋白1（Drp 1）调节线粒体膜动力学。Rab 32还被报道诱导自噬，这是一种靶向细胞内组分降解的重要途径。然而，Rab 32没有自噬特异性效应子。类似地，这种小GTdR靶向的细胞内膜的身份及其诱导的自噬类型尚不清楚。为了研究Rab 32介导的自噬降解的靶点，我们测试了一大组细胞器蛋白。我们发现MERC蛋白的一个子集，包括硫氧还蛋白相关的跨膜蛋白TMX 1，是以Rab 32依赖性方式特异性降解的靶点。我们还确定了Reticulon-3（RTN 3L）的长亚型，一种已知的ER-吞噬受体，作为Rab 32效应器。Rab 32在RTN 3L的帮助下通过自噬促进近端内质网膜的降解。我们建议将这种类型的选择性自噬称为“MAM-phagy”。在线版本包含补充材料，可通过10.1186/s13062-021-00311-9获得。
Rab32 is a small GTPase associated with multiple organelles but is particularly enriched at the endoplasmic reticulum (ER). Here, it controls targeting to mitochondria-ER contacts (MERCs), thus influencing composition of the mitochondria-associated membrane (MAM). Moreover, Rab32 regulates mitochondrial membrane dynamics via its effector dynamin-related protein 1 (Drp1). Rab32 has also been reported to induce autophagy, an essential pathway targeting intracellular components for their degradation. However, no autophagy-specific effectors have been identified for Rab32. Similarly, the identity of the intracellular membrane targeted by this small GTPase and the type of autophagy it induces are not known yet. To investigate the target of autophagic degradation mediated by Rab32, we tested a large panel of organellar proteins. We found that a subset of MERC proteins, including the thioredoxin-related transmembrane protein TMX1, are specifically targeted for degradation in a Rab32-dependent manner. We also identified the long isoform of reticulon-3 (RTN3L), a known ER-phagy receptor, as a Rab32 effector. Rab32 promotes degradation of mitochondrial-proximal ER membranes through autophagy with the help of RTN3L. We propose to call this type of selective autophagy “MAM-phagy”. The online version contains supplementary material available at 10.1186/s13062-021-00311-9.
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影响因子：
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作者：
Fregno I;Molinari M
通讯作者：
Molinari M
DOI：
10.1083/jcb.200204081
发表时间：
2002-08-19
期刊：
The Journal of cell biology
影响因子：
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