Hoffmann Anke, Spengler Dietmar
Epigenomics of Early Life, Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
Front Behav Neurosci. 2018 Dec 6;12:306. doi: 10.3389/fnbeh.2018.00306. eCollection 2018.
Mitochondria play a central role in cellular energy-generating processes and are master regulators of cell life. They provide the energy necessary to reinstate and sustain homeostasis in response to stress, and to launch energy intensive adaptation programs to ensure an organism's survival and future well-being. By this means, mitochondria are particularly apt to mediate brain programming by early-life stress (ELS) and to serve at the same time as subcellular substrate in the programming process. With a focus on mitochondria's integrated role in metabolism, steroidogenesis and oxidative stress, we review current findings on altered mitochondrial function in the brain, the placenta and peripheral blood cells following ELS-dependent programming in rodents and recent insights from humans exposed to early life adversity (ELA). Concluding, we propose a role of the mitochondrion as subcellular intersection point connecting ELS, brain programming and mental well-being, and a role as a potential site for therapeutic interventions in individuals exposed to severe ELS.
线粒体在细胞能量生成过程中发挥核心作用,是细胞生命的主要调节者。它们提供能量,以恢复和维持应激状态下的内环境稳态,并启动能量密集型适应程序,以确保生物体的生存和未来健康。通过这种方式,线粒体特别容易介导早期生活应激(ELS)对大脑的编程作用,同时在编程过程中作为亚细胞底物发挥作用。我们聚焦于线粒体在代谢、类固醇生成和氧化应激中的综合作用,回顾了啮齿动物在ELS依赖性编程后大脑、胎盘和外周血细胞中线粒体功能改变的当前研究结果,以及近期来自经历早期生活逆境(ELA)的人类的见解。最后,我们提出线粒体作为连接ELS、大脑编程和心理健康的亚细胞交汇点的作用,以及作为严重ELS个体治疗干预潜在位点的作用。