Matches in SemOpenAlex for { <https://semopenalex.org/work/W4312129352> ?p ?o ?g. }
- W4312129352 endingPage "243" @default.
- W4312129352 startingPage "229" @default.
- W4312129352 abstract "Ubiquinol cytochrome c reductase hinge protein (UQCRH) is required for the electron transfer between cytochrome c1 and c of the mitochondrial cytochrome bc1 Complex (CIII). A two-exon deletion in the human UQCRH gene has recently been identified as the cause for a rare familial mitochondrial disorder. Deletion of the corresponding gene in the mouse (Uqcrh-KO) resulted in striking biochemical and clinical similarities including impairment of CIII, failure to thrive, elevated blood glucose levels, and early death. Here, we set out to test how global ablation of the murine Uqcrh affects cardiac morphology and contractility, and bioenergetics. Hearts from Uqcrh-KO mutant mice appeared macroscopically considerably smaller compared to wildtype littermate controls despite similar geometries as confirmed by transthoracic echocardiography (TTE). Relating TTE-assessed heart to body mass revealed the development of subtle cardiac enlargement, but histopathological analysis showed no excess collagen deposition. Nonetheless, Uqcrh-KO hearts developed pronounced contractile dysfunction. To assess mitochondrial functions, we used the high-resolution respirometer NextGen-O2k allowing measurement of mitochondrial respiratory capacity through the electron transfer system (ETS) simultaneously with the redox state of ETS-reactive coenzyme Q (Q), or production of reactive oxygen species (ROS). Compared to wildtype littermate controls, we found decreased mitochondrial respiratory capacity and more reduced Q in Uqcrh-KO, indicative for an impaired ETS. Yet, mitochondrial ROS production was not generally increased. Taken together, our data suggest that Uqcrh-KO leads to cardiac contractile dysfunction at 9 weeks of age, which is associated with impaired bioenergetics but not with mitochondrial ROS production. Global ablation of the Uqcrh gene results in functional impairment of CIII associated with metabolic dysfunction and postnatal developmental arrest immediately after weaning from the mother. Uqcrh-KO mice show dramatically elevated blood glucose levels and decreased ability of isolated cardiac mitochondria to consume oxygen (O2). Impaired development (failure to thrive) after weaning manifests as a deficiency in the gain of body mass and growth of internal organ including the heart. The relative heart mass seemingly increases when organ mass calculated from transthoracic echocardiography (TTE) is normalized to body mass. Notably, the heart shows no signs of collagen deposition, yet does develop a contractile dysfunction reflected by a decrease in ejection fraction and fractional shortening." @default.
- W4312129352 created "2023-01-04" @default.
- W4312129352 creator A5004472037 @default.
- W4312129352 creator A5005212460 @default.
- W4312129352 creator A5015518003 @default.
- W4312129352 creator A5016193571 @default.
- W4312129352 creator A5016492928 @default.
- W4312129352 creator A5018729995 @default.
- W4312129352 creator A5022557991 @default.
- W4312129352 creator A5027563058 @default.
- W4312129352 creator A5039721950 @default.
- W4312129352 creator A5060773111 @default.
- W4312129352 creator A5062258378 @default.
- W4312129352 creator A5072081106 @default.
- W4312129352 creator A5073485396 @default.
- W4312129352 creator A5077857985 @default.
- W4312129352 date "2022-12-24" @default.
- W4312129352 modified "2023-10-18" @default.
- W4312129352 title "Knockout of the Complex III subunit Uqcrh causes bioenergetic impairment and cardiac contractile dysfunction" @default.
- W4312129352 cites W1508063700 @default.
- W4312129352 cites W1600613094 @default.
- W4312129352 cites W1615555718 @default.
- W4312129352 cites W1638874881 @default.
- W4312129352 cites W1938258474 @default.
- W4312129352 cites W1971972136 @default.
- W4312129352 cites W1980267283 @default.
- W4312129352 cites W1987097693 @default.
- W4312129352 cites W1995496906 @default.
- W4312129352 cites W2007102240 @default.
- W4312129352 cites W2017109450 @default.
- W4312129352 cites W2021065127 @default.
- W4312129352 cites W2039734446 @default.
- W4312129352 cites W2040287423 @default.
- W4312129352 cites W2052884790 @default.
- W4312129352 cites W2053896137 @default.
- W4312129352 cites W2055066000 @default.
- W4312129352 cites W2069931528 @default.
- W4312129352 cites W2071518542 @default.
- W4312129352 cites W2082531877 @default.
- W4312129352 cites W2105137428 @default.
- W4312129352 cites W2125090847 @default.
- W4312129352 cites W2128606426 @default.
- W4312129352 cites W2128653444 @default.
- W4312129352 cites W2144192671 @default.
- W4312129352 cites W2173980345 @default.
- W4312129352 cites W2335788856 @default.
- W4312129352 cites W2398202798 @default.
- W4312129352 cites W2409659318 @default.
- W4312129352 cites W2518572704 @default.
- W4312129352 cites W2565443325 @default.
- W4312129352 cites W2598089221 @default.
- W4312129352 cites W2760369630 @default.
- W4312129352 cites W2799333965 @default.
- W4312129352 cites W2806334045 @default.
- W4312129352 cites W2808184177 @default.
- W4312129352 cites W2884533811 @default.
- W4312129352 cites W2885025259 @default.
- W4312129352 cites W2886044379 @default.
- W4312129352 cites W2905405688 @default.
- W4312129352 cites W2971584098 @default.
- W4312129352 cites W2995460565 @default.
- W4312129352 cites W2997046468 @default.
- W4312129352 cites W3004889911 @default.
- W4312129352 cites W3022086981 @default.
- W4312129352 cites W3138401678 @default.
- W4312129352 cites W3212249862 @default.
- W4312129352 cites W4210476933 @default.
- W4312129352 cites W4211163242 @default.
- W4312129352 cites W4284961706 @default.
- W4312129352 cites W4285242698 @default.
- W4312129352 doi "https://doi.org/10.1007/s00335-022-09973-w" @default.
- W4312129352 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36565314" @default.
- W4312129352 hasPublicationYear "2022" @default.
- W4312129352 type Work @default.
- W4312129352 citedByCount "0" @default.
- W4312129352 crossrefType "journal-article" @default.
- W4312129352 hasAuthorship W4312129352A5004472037 @default.
- W4312129352 hasAuthorship W4312129352A5005212460 @default.
- W4312129352 hasAuthorship W4312129352A5015518003 @default.
- W4312129352 hasAuthorship W4312129352A5016193571 @default.
- W4312129352 hasAuthorship W4312129352A5016492928 @default.
- W4312129352 hasAuthorship W4312129352A5018729995 @default.
- W4312129352 hasAuthorship W4312129352A5022557991 @default.
- W4312129352 hasAuthorship W4312129352A5027563058 @default.
- W4312129352 hasAuthorship W4312129352A5039721950 @default.
- W4312129352 hasAuthorship W4312129352A5060773111 @default.
- W4312129352 hasAuthorship W4312129352A5062258378 @default.
- W4312129352 hasAuthorship W4312129352A5072081106 @default.
- W4312129352 hasAuthorship W4312129352A5073485396 @default.
- W4312129352 hasAuthorship W4312129352A5077857985 @default.
- W4312129352 hasBestOaLocation W43121293521 @default.
- W4312129352 hasConcept C100206155 @default.
- W4312129352 hasConcept C104317684 @default.
- W4312129352 hasConcept C126322002 @default.
- W4312129352 hasConcept C134018914 @default.
- W4312129352 hasConcept C14471203 @default.
- W4312129352 hasConcept C24586158 @default.
- W4312129352 hasConcept C2777614518 @default.