Koji Yamano, Chunxin Wang, Shireen A. Sarraf, Christian Münch, Reika Kikuchi, Nobuo N. Noda, Yohei Hizukuri, Masato T. Kanemaki, Wade Harper, Keiji Tanaka, Noriyuki Matsuda, Richard J. Youle
- Damaged mitochondria are selectively eliminated by mitophagy. Parkin and PINK1, gene products mutated in familial Parkinson’s disease, play essential roles in mitophagy through ubiquitination of mitochondria. Cargo ubiquitination by E3 ubiquitin ligase Parkin is important to trigger selective autophagy. Although autophagy receptors recruit LC3-labeled autophagic membranes onto damaged mitochondria, how other essential autophagy units such as ATG9A-integrated vesicles are recruited remains unclear. Here, using mammalian cultured cells, we demonstrate that RABGEF1, the upstream factor of the endosomal Rab GTPase cascade, is recruited to damaged mitochondria via ubiquitin binding downstream of Parkin. 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. These results strongly suggest that endosomal Rab cycles on damaged mitochondria are a crucial regulator of mitophagy through assembling ATG9A vesicles.
MetadatenAuthor: | Koji Yamano, Chunxin Wang, Shireen A. Sarraf, Christian MünchORCiD, Reika Kikuchi, Nobuo N. Noda, Yohei Hizukuri, Masato T. Kanemaki, Wade Harper, Keiji Tanaka, Noriyuki Matsuda, Richard J. Youle |
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URN: | urn:nbn:de:hebis:30:3-477327 |
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DOI: | https://doi.org/10.7554/eLife.31326.001 |
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ISSN: | 2050-084X |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/29360040 |
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Parent Title (English): | eLife |
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Publisher: | eLife Sciences Publications |
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Place of publication: | Cambridge |
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Contributor(s): | Ivan Đikić |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2018 |
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Date of first Publication: | 2018/01/23 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2018/10/25 |
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Tag: | Parkin; Rab7; Research article; autophagy; cell biology; human; mitochondria; ubiquitin |
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Volume: | 7 |
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Issue: | e31326 |
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Page Number: | 32 |
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First Page: | 1 |
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Last Page: | 32 |
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Note: | Copyright Yamano et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
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HeBIS-PPN: | 439098335 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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