| http://purl.uniprot.org/citations/31676548 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31676548 | http://www.w3.org/2000/01/rdf-schema#comment | "Elimination of dysfunctional mitochondria via mitophagy is essential for cell survival and neuronal functions. But, how impaired mitophagy participates in tissue-specific vulnerability in the brain remains unclear. Here, we find that striatal-enriched protein, Rhes, is a critical regulator of mitophagy and striatal vulnerability in brain. In vivo interactome and density fractionation reveal that Rhes coimmunoprecipitates and cosediments with mitochondrial and lysosomal proteins. Live-cell imaging of cultured striatal neuronal cell line shows Rhes surrounds globular mitochondria, recruits lysosomes, and ultimately degrades mitochondria. In the presence of 3-nitropropionic acid (3-NP), an inhibitor of succinate dehydrogenase, Rhes disrupts mitochondrial membrane potential (ΔΨ m ) and promotes excessive mitophagy and cell death. Ultrastructural analysis reveals that systemic injection of 3-NP in mice promotes globular mitochondria, accumulation of mitophagosomes, and striatal lesion only in the wild-type (WT), but not in the Rhes knockout (KO), striatum, suggesting that Rhes is critical for mitophagy and neuronal death in vivo. Mechanistically, Rhes requires Nix (BNIP3L), a known receptor of mitophagy, to disrupt ΔΨ m and promote mitophagy and cell death. Rhes interacts with Nix via SUMO E3-ligase domain, and Nix depletion totally abrogates Rhes-mediated mitophagy and cell death in the cultured striatal neuronal cell line. Finally, we find that Rhes, which travels from cell to cell via tunneling nanotube (TNT)-like cellular protrusions, interacts with dysfunctional mitochondria in the neighboring cell in a Nix-dependent manner. Collectively, Rhes is a major regulator of mitophagy via Nix, which may determine striatal vulnerability in the brain."xsd:string |
| http://purl.uniprot.org/citations/31676548 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1912868116"xsd:string |
| http://purl.uniprot.org/citations/31676548 | http://purl.uniprot.org/core/author | "Tapia R."xsd:string |
| http://purl.uniprot.org/citations/31676548 | http://purl.uniprot.org/core/author | "Subramaniam S."xsd:string |
| http://purl.uniprot.org/citations/31676548 | http://purl.uniprot.org/core/author | "Sharma M."xsd:string |
| http://purl.uniprot.org/citations/31676548 | http://purl.uniprot.org/core/author | "Sharma V."xsd:string |
| http://purl.uniprot.org/citations/31676548 | http://purl.uniprot.org/core/author | "Kazantzis M."xsd:string |
| http://purl.uniprot.org/citations/31676548 | http://purl.uniprot.org/core/author | "Eshraghi M."xsd:string |
| http://purl.uniprot.org/citations/31676548 | http://purl.uniprot.org/core/author | "Shahani N."xsd:string |
| http://purl.uniprot.org/citations/31676548 | http://purl.uniprot.org/core/author | "Rivera O."xsd:string |
| http://purl.uniprot.org/citations/31676548 | http://purl.uniprot.org/core/author | "Ramirez Jarquin U.N."xsd:string |
| http://purl.uniprot.org/citations/31676548 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/31676548 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/31676548 | http://purl.uniprot.org/core/pages | "23760-23771"xsd:string |
| http://purl.uniprot.org/citations/31676548 | http://purl.uniprot.org/core/title | "Rhes, a striatal-enriched protein, promotes mitophagy via Nix."xsd:string |
| http://purl.uniprot.org/citations/31676548 | http://purl.uniprot.org/core/volume | "116"xsd:string |
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