| http://purl.uniprot.org/citations/35015731 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35015731 | http://www.w3.org/2000/01/rdf-schema#comment | "Mitophagy and mitochondrial integrated stress response (ISR) are 2 primary protective mechanisms to maintain functional mitochondria. Whether these 2 processes are coordinately regulated remains unclear. Here we show that mitochondrial fission 1 protein (Fis1), which is required for completion of mitophagy, serves as a signaling hub linking mitophagy and ISR. In mouse hepatocytes, high fat diet (HFD) feeding induces unresolved oxidative stress, defective mitophagy and enhanced type I interferon (IFN-I) response implicated in promoting metabolic inflammation. Adenoviral-mediated acute hepatic Fis1 overexpression is sufficient to reduce oxidative damage and improve glucose homeostasis in HFD-fed mice. RNA-Seq analysis reveals that Fis1 triggers a retrograde mitochondria-to-nucleus communication upregulating ISR genes encoding anti-oxidant defense, redox homeostasis, and proteostasis pathways. Fis1-mediated ISR also suppresses expression of IFN-I-stimulated genes through activating transcription factor 5 (Atf5), which inhibits the transactivation activity of interferon regulatory factor 3 (Irf3) known to control IFN-I production. Metabolite analysis demonstrates that Fis1 activation leads to accumulation of fumarate, a TCA cycle intermediate capable of increasing Atf5 activity. Consequently, hepatic Atf5 overexpression or monomethyl fumarate (MMF) treatment improves glucose homeostasis in HFD-fed mice. Collectively, these results support the potential use of small molecules targeting the Fis1-Atf5 axis, such as MMF, to treat metabolic diseases."xsd:string |
| http://purl.uniprot.org/citations/35015731 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci.insight.150041"xsd:string |
| http://purl.uniprot.org/citations/35015731 | http://purl.uniprot.org/core/author | "Lee C.H."xsd:string |
| http://purl.uniprot.org/citations/35015731 | http://purl.uniprot.org/core/author | "Knudsen N.H."xsd:string |
| http://purl.uniprot.org/citations/35015731 | http://purl.uniprot.org/core/author | "Liou Y.H."xsd:string |
| http://purl.uniprot.org/citations/35015731 | http://purl.uniprot.org/core/author | "Jacobi D."xsd:string |
| http://purl.uniprot.org/citations/35015731 | http://purl.uniprot.org/core/author | "Nnah I.C."xsd:string |
| http://purl.uniprot.org/citations/35015731 | http://purl.uniprot.org/core/author | "Chalom M.M."xsd:string |
| http://purl.uniprot.org/citations/35015731 | http://purl.uniprot.org/core/author | "Starost K.A."xsd:string |
| http://purl.uniprot.org/citations/35015731 | http://purl.uniprot.org/core/author | "Personnaz J."xsd:string |
| http://purl.uniprot.org/citations/35015731 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35015731 | http://purl.uniprot.org/core/name | "JCI Insight"xsd:string |
| http://purl.uniprot.org/citations/35015731 | http://purl.uniprot.org/core/pages | "e150041"xsd:string |
| http://purl.uniprot.org/citations/35015731 | http://purl.uniprot.org/core/title | "Hepatic Fis1 regulates mitochondrial integrated stress response and improves metabolic homeostasis."xsd:string |
| http://purl.uniprot.org/citations/35015731 | http://purl.uniprot.org/core/volume | "7"xsd:string |
| http://purl.uniprot.org/citations/35015731 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/35015731 |
| http://purl.uniprot.org/citations/35015731 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/35015731 |
| http://purl.uniprot.org/uniprot/#_D3YZ32-mappedCitation-35015731 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35015731 |
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| http://purl.uniprot.org/uniprot/#_Q9CQ92-mappedCitation-35015731 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35015731 |
| http://purl.uniprot.org/uniprot/Q9CQ92 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/35015731 |
| http://purl.uniprot.org/uniprot/G3X9U9 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/35015731 |
| http://purl.uniprot.org/uniprot/D3YZ32 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/35015731 |