2023年7月19日 · We found that parkin regulates mitochondria-lysosome tethering via stabilization of active, lysosome-bound Rab7, while knockdown of the Rab7 GAP TBC1D15 was sufficient to reestablish proper mitochondria-lysosome contact tethering in parkin PD neurons.

2018年1月23日 · RABGEF1 directs the downstream Rab proteins, RAB5 and RAB7A, to damaged mitochondria, whose associations are further regulated by mitochondrial Rab-GAPs. Furthermore, depletion of RAB7A inhibited ATG9A vesicle assembly and subsequent encapsulation of the mitochondria by autophagic membranes.

2018年1月23日 · In this study, we show that RABGEF1, a guanine nucleotide exchange factor (GEF) of endosomal Rab proteins, which contains UBDs, is recruited to damaged mitochondria in a Parkin-dependent manner. RABGEF1 directs the downstream Rab proteins, RAB5 and RAB7A, to damaged mitochondria, that is further regulated by mitochondrial Rab-GAPs.

Removal of damaged mitochondria is orchestrated by a pathway involving the PINK1 kinase and the PARKIN ubiquitin ligase. Ubiquitin chains assembled by PARKIN on the mitochondrial outer membrane recruit autophagy cargo receptors in complexes with TBK1 protein kinase.

2018年11月21日 · Removal of damaged mitochondria is orchestrated by a pathway involving the PINK1 kinase and the PARKIN ubiquitin ligase. Ubiquitin chains assembled by PARKIN on the mitochondrial outer membrane recruit autophagy cargo …

We showed that LRRK1 functions downstream of ULK1 and ULK2 in Parkin-mediated mitophagy. Furthermore, we demonstrated that ectopic targeting of active LRRK1 to mitochondria is sufficient to induce the Ser-72 phosphorylation of Rab7, circumventing the requirement for ATG13, a component of the ULK complex.

2016年2月2日 · Although Rab7 has been suggested to be involved in mediating Parkin function as an effector of TBC1D15 and TBC1D17 to regulate autophagosome morphogenesis (Yamano et al., 2014), our study reveals another important aspect of Parkin-dependent modulation of endo-lysosomal pathway: ubiquitination of Rab7 directly on K38 residue and regulation of ...

2016年7月14日 · We find that PINK1 and Parkin, two mitochondrial proteins linked to Parkinson’s disease (PD), actively inhibit MDV formation and MitAP. In absence of PINK1 or Parkin, inflammatory conditions trigger MitAP in immune cells, both in vitro and in vivo.

2020年12月9日 · Rab7蛋白参与了线粒体和溶酶体相互作用过程中的关键环节，包括早期驱动富含Atg9A的膜结构形成吞噬泡包裹损伤的线粒体，介导PINK1/Parkin依赖的线粒体自噬体形成；线粒体自噬体与溶酶体融合；介导线粒体-溶酶体接触与解离的过程，进而双向调控线粒体与溶酶体 ...

2022年12月1日 · We showed that LRRK1 functions downstream of ULK1 and ULK2 in Parkin-mediated mitophagy. Furthermore, we demonstrated that ectopic targeting of active LRRK1 to mitochondria is sufficient to induce the Ser-72 phosphorylation of Rab7, circumventing the requirement for ATG13, a component of the ULK complex.