Matches in SemOpenAlex for { <https://semopenalex.org/work/W3149167905> ?p ?o ?g. }
- W3149167905 abstract "Abstract Mitochondrial DNA (mtDNA) has been suggested to drive immune system activation, but the induction of interferon signaling by mtDNA has not been demonstrated in a Mendelian mitochondrial disease. We initially ascertained two patients, one with a purely neurological phenotype, and one with features suggestive of systemic sclerosis in a syndromic context, and found them both to demonstrate enhanced interferon-stimulated gene (ISG) expression in blood. We determined each to harbor a previously described de novo dominant-negative heterozygous mutation in ATAD3A , encoding ATPase family AAA domain-containing protein 3A (ATAD3A). We identified five further patients with mutations in ATAD3A , and recorded up-regulated ISG expression and interferon alpha protein in four of them. Knockdown of ATAD3A in THP-1 cells resulted in increased interferon signaling, mediated by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Enhanced interferon signaling was abrogated in THP-1 cells and patient fibroblasts depleted of mtDNA. Thus, mutations in the mitochondrial membrane protein ATAD3A define a novel type I interferonopathy. Summary Dominant-negative mutations in ATAD3A, a ubiquitously expressed mitochondrial protein, cause mitochondrial DNA-dependent up-regulation of type I interferon signaling in the context of neurological disease and autoimmunity, thereby defining a novel type I interferonopathy." @default.
- W3149167905 created "2021-04-13" @default.
- W3149167905 creator A5002274576 @default.
- W3149167905 creator A5004073759 @default.
- W3149167905 creator A5004618232 @default.
- W3149167905 creator A5013758087 @default.
- W3149167905 creator A5014084371 @default.
- W3149167905 creator A5017916851 @default.
- W3149167905 creator A5020878577 @default.
- W3149167905 creator A5022787939 @default.
- W3149167905 creator A5024422532 @default.
- W3149167905 creator A5025524692 @default.
- W3149167905 creator A5026011465 @default.
- W3149167905 creator A5032325627 @default.
- W3149167905 creator A5038538377 @default.
- W3149167905 creator A5041040586 @default.
- W3149167905 creator A5041910711 @default.
- W3149167905 creator A5042731682 @default.
- W3149167905 creator A5046909004 @default.
- W3149167905 creator A5059314455 @default.
- W3149167905 creator A5059840607 @default.
- W3149167905 creator A5063570436 @default.
- W3149167905 creator A5064465434 @default.
- W3149167905 creator A5070915135 @default.
- W3149167905 creator A5076289755 @default.
- W3149167905 creator A5080499234 @default.
- W3149167905 creator A5081327741 @default.
- W3149167905 creator A5081868780 @default.
- W3149167905 creator A5082661470 @default.
- W3149167905 creator A5083510818 @default.
- W3149167905 creator A5084551365 @default.
- W3149167905 creator A5085574055 @default.
- W3149167905 date "2021-04-03" @default.
- W3149167905 modified "2023-09-30" @default.
- W3149167905 title "Enhanced cGAS-STING-dependent interferon signaling associated with mutations in ATAD3A" @default.
- W3149167905 cites W1542158376 @default.
- W3149167905 cites W1946982336 @default.
- W3149167905 cites W1966676847 @default.
- W3149167905 cites W1985538633 @default.
- W3149167905 cites W1985990508 @default.
- W3149167905 cites W1997801295 @default.
- W3149167905 cites W2015879727 @default.
- W3149167905 cites W2030785379 @default.
- W3149167905 cites W2035232303 @default.
- W3149167905 cites W2035752440 @default.
- W3149167905 cites W2063675796 @default.
- W3149167905 cites W2116852197 @default.
- W3149167905 cites W2126385937 @default.
- W3149167905 cites W2133572194 @default.
- W3149167905 cites W2138282259 @default.
- W3149167905 cites W2186721808 @default.
- W3149167905 cites W2202022139 @default.
- W3149167905 cites W2508060872 @default.
- W3149167905 cites W2520289738 @default.
- W3149167905 cites W2584025181 @default.
- W3149167905 cites W2606232917 @default.
- W3149167905 cites W2619794108 @default.
- W3149167905 cites W2754142482 @default.
- W3149167905 cites W2782929501 @default.
- W3149167905 cites W2788480107 @default.
- W3149167905 cites W2790466592 @default.
- W3149167905 cites W2883018577 @default.
- W3149167905 cites W2883721603 @default.
- W3149167905 cites W2909164374 @default.
- W3149167905 cites W2913512379 @default.
- W3149167905 cites W2923815119 @default.
- W3149167905 cites W2925205243 @default.
- W3149167905 cites W2952276447 @default.
- W3149167905 cites W2980294595 @default.
- W3149167905 cites W2982511147 @default.
- W3149167905 cites W2987579732 @default.
- W3149167905 cites W2994831269 @default.
- W3149167905 cites W2996537134 @default.
- W3149167905 cites W2996886630 @default.
- W3149167905 cites W3003301787 @default.
- W3149167905 cites W3033954889 @default.
- W3149167905 cites W3045749034 @default.
- W3149167905 cites W3083914771 @default.
- W3149167905 cites W3092551839 @default.
- W3149167905 cites W3093008524 @default.
- W3149167905 cites W3118659380 @default.
- W3149167905 doi "https://doi.org/10.1101/2021.04.02.438201" @default.
- W3149167905 hasPublicationYear "2021" @default.
- W3149167905 type Work @default.
- W3149167905 sameAs 3149167905 @default.
- W3149167905 citedByCount "0" @default.
- W3149167905 crossrefType "posted-content" @default.
- W3149167905 hasAuthorship W3149167905A5002274576 @default.
- W3149167905 hasAuthorship W3149167905A5004073759 @default.
- W3149167905 hasAuthorship W3149167905A5004618232 @default.
- W3149167905 hasAuthorship W3149167905A5013758087 @default.
- W3149167905 hasAuthorship W3149167905A5014084371 @default.
- W3149167905 hasAuthorship W3149167905A5017916851 @default.
- W3149167905 hasAuthorship W3149167905A5020878577 @default.
- W3149167905 hasAuthorship W3149167905A5022787939 @default.
- W3149167905 hasAuthorship W3149167905A5024422532 @default.
- W3149167905 hasAuthorship W3149167905A5025524692 @default.
- W3149167905 hasAuthorship W3149167905A5026011465 @default.
- W3149167905 hasAuthorship W3149167905A5032325627 @default.
- W3149167905 hasAuthorship W3149167905A5038538377 @default.