Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis.
Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis.
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DOI：
10.1016/j.neuron.2016.12.017
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发表时间：
2017-02-08
期刊：
影响因子：
16.2
通讯作者：
Lie DC
中科院分区：
文献类型：
--
作者：
Beckervordersandforth R;Ebert B;Schäffner I;Moss J;Fiebig C;Shin J;Moore DL;Ghosh L;Trinchero MF;Stockburger C;Friedland K;Steib K;von Wittgenstein J;Keiner S;Redecker C;Hölter SM;Xiang W;Wurst W;Jagasia R;Schinder AF;Ming GL;Toni N;Jessberger S;Song H;Lie DC
细胞代谢的精确调节被假设为构成海马神经元从静止神经干细胞（NSCs）终身生成的发育序列的重要组成部分。阶段特异性代谢程序的身份及其对成人神经发生的影响在很大程度上是未知的。我们发现，成人海马神经源性谱系是严重依赖于线粒体电子传递链和氧化磷酸化机制的快速增殖的中间祖细胞的阶段。通过消融线粒体转录因子A（Tfam）来干扰线粒体复合体功能，重现了海马神经发生中的多种衰老标志，而线粒体功能的药理学增强改善了与年龄相关的神经发生缺陷。与年龄相关的线粒体功能和形态学在神经干细胞中的改变的发现一起，这些数据将线粒体复合体功能与成年神经干细胞的有效谱系进展联系起来，并将线粒体功能鉴定为改善衰老海马中神经发生缺陷的潜在靶点。
Precise regulation of cellular metabolism is hypothesized to constitute a vital component of the developmental sequence underlying the life-long generation of hippocampal neurons from quiescent neural stem cells (NSCs). The identity of stage-specific metabolic programs and their impact on adult neurogenesis are largely unknown. We show that the adult hippocampal neurogenic lineage is critically dependent on the mitochondrial electron transport chain and oxidative phosphorylation machinery at the stage of the fast proliferating intermediate progenitor cell. Perturbation of mitochondrial complex function by ablation of the mitochondrial transcription factor A (Tfam) reproduces multiple hallmarks of aging in hippocampal neurogenesis, whereas pharmacological enhancement of mitochondrial function ameliorates age-associated neurogenesis defects. Together with the finding of age-associated alterations in mitochondrial function and morphology in NSCs, these data link mitochondrial complex function to efficient lineage progression of adult NSCs and identify mitochondrial function as a potential target to ameliorate neurogenesis-defects in the aging hippocampus.