The Chchd10 gene encodes a coiled-coil-helix-coiled-coil-helix-domain containing protein predicted to function in the mitochondrion and nucleus.Mutations of Chchd10 are associated with ALS,dementia and myopathy in hum...The Chchd10 gene encodes a coiled-coil-helix-coiled-coil-helix-domain containing protein predicted to function in the mitochondrion and nucleus.Mutations of Chchd10 are associated with ALS,dementia and myopathy in humans and animal models,but how knockout of Chchd10(Chchd10KO)affects various tissues especially skeletal muscle and adipose tissues remains unclear.Here we show that Chchd10 expression increases as myoblasts and preadipocytes dif-ferentiate.During myogenesis,CHCHD10 interacts with TAR DNA binding protein 43(TDP-43)in regenerating myofib-ers in vivo and in newly differentiated myotubes ex vivo.Surprisingly,Chchd10KO mice had normal skeletal muscle development,growth and regeneration,with moderate defects in grip strength and motor performance.Chchd10KO similarly had no effects on development of brown and white adipose tissues(WAT).However,Chchd10KO mice had blunted response to acute cold and attenuated cold-induced browning of WAT,with markedly reduced UCP1 levels.Together,these results demonstrate that Chchd10 is dispensable for normal myogenesis and adipogenesis but is required for normal motility and cold-induced,mitochondrion-dependent browning of adipocytes.The data also sug-gest that human CHCHD10 mutations cause myopathy through a gain-of-function mechanism.展开更多
基金This work was supported by the Young Scientists Fund of the National Natural Science Foundation of China(31900586)Special project for talents enrollment of Hebei Agricultural University(YJ2021013)to WXpartially through United States Department of Agriculture(NC-1184)to SK.
文摘The Chchd10 gene encodes a coiled-coil-helix-coiled-coil-helix-domain containing protein predicted to function in the mitochondrion and nucleus.Mutations of Chchd10 are associated with ALS,dementia and myopathy in humans and animal models,but how knockout of Chchd10(Chchd10KO)affects various tissues especially skeletal muscle and adipose tissues remains unclear.Here we show that Chchd10 expression increases as myoblasts and preadipocytes dif-ferentiate.During myogenesis,CHCHD10 interacts with TAR DNA binding protein 43(TDP-43)in regenerating myofib-ers in vivo and in newly differentiated myotubes ex vivo.Surprisingly,Chchd10KO mice had normal skeletal muscle development,growth and regeneration,with moderate defects in grip strength and motor performance.Chchd10KO similarly had no effects on development of brown and white adipose tissues(WAT).However,Chchd10KO mice had blunted response to acute cold and attenuated cold-induced browning of WAT,with markedly reduced UCP1 levels.Together,these results demonstrate that Chchd10 is dispensable for normal myogenesis and adipogenesis but is required for normal motility and cold-induced,mitochondrion-dependent browning of adipocytes.The data also sug-gest that human CHCHD10 mutations cause myopathy through a gain-of-function mechanism.
