J. Gothié, Anthony Sébillot, C. Luongo, M. Legendre, Marine Perret-Jeanneret, K. L. Blay, S. Remaud, B. Demeneix
{"title":"Mitochondrial metabolism and thyroid hormones: a game of influence over adult neural stem cell fate decision?","authors":"J. Gothié, Anthony Sébillot, C. Luongo, M. Legendre, Marine Perret-Jeanneret, K. L. Blay, S. Remaud, B. Demeneix","doi":"10.18143/JWMS_V2I2_1963","DOIUrl":null,"url":null,"abstract":"Unlike differentiated cells, stem cells use aerobic glycosylation rather than oxidative phosphorylation1. Moreover, metabolic status influences stem cell determination2. Thyroid hormones (THs) regulate neural stem cell (NSC) commitment towards a neuronal phenotype in adult brain3, but also have major roles in mitochondrial metabolism4. Given these complimentary roles, we investigated the convergence of THs and mitochondrial metabolism on NSC fate determination towards neuronal or glial fate. Following stereotaxic injection of the mitochondrial membrane potential marker (JC-1) into the adult mouse lateral ventricle, we observed greater mitochondrial activity in cells committed toward a neuronal than an oligodendroglial phenotype. Further, in vitro studies in neurospheres using a dye revealing ROS production (hydroethidine) show that THs increase ROS production and promote neuronal determination. These studies also showed that the activated form of DRP1 (pDRP1S616), mediating mitochondrial fission, is preferentially detected in the cytosol of neuronal lineage cells. Together, these results show that both THs and mitochondrial activity impact NSCs fate decision. We hypothesize that THs govern NSCs commitment through their effects on mitochondria. Future work will address the impact of modulating DRP1 expression in different thyroid contexts. This work should provide new insights into the mechanisms governing adult NSCs fate.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"73 1","pages":"0"},"PeriodicalIF":0.0000,"publicationDate":"2016-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of World Mitochondria Society","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.18143/JWMS_V2I2_1963","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Unlike differentiated cells, stem cells use aerobic glycosylation rather than oxidative phosphorylation1. Moreover, metabolic status influences stem cell determination2. Thyroid hormones (THs) regulate neural stem cell (NSC) commitment towards a neuronal phenotype in adult brain3, but also have major roles in mitochondrial metabolism4. Given these complimentary roles, we investigated the convergence of THs and mitochondrial metabolism on NSC fate determination towards neuronal or glial fate. Following stereotaxic injection of the mitochondrial membrane potential marker (JC-1) into the adult mouse lateral ventricle, we observed greater mitochondrial activity in cells committed toward a neuronal than an oligodendroglial phenotype. Further, in vitro studies in neurospheres using a dye revealing ROS production (hydroethidine) show that THs increase ROS production and promote neuronal determination. These studies also showed that the activated form of DRP1 (pDRP1S616), mediating mitochondrial fission, is preferentially detected in the cytosol of neuronal lineage cells. Together, these results show that both THs and mitochondrial activity impact NSCs fate decision. We hypothesize that THs govern NSCs commitment through their effects on mitochondria. Future work will address the impact of modulating DRP1 expression in different thyroid contexts. This work should provide new insights into the mechanisms governing adult NSCs fate.