Development, Health and Disease Research Program, School of Medicine, Irvine, CA, USA.
Department of Pediatrics, School of Medicine, Irvine, CA, USA.
Proc Biol Sci. 2020 May 13;287(1926):20192713. doi: 10.1098/rspb.2019.2713. Epub 2020 Apr 29.
Research on mechanisms underlying the phenomenon of developmental programming of health and disease has focused primarily on processes that are specific to cell types, organs and phenotypes of interest. However, the observation that exposure to suboptimal or adverse developmental conditions influences a broad range of phenotypes suggests that these exposures may additionally exert effects through cellular mechanisms that are common, or shared, across these different cell and tissue types. It is in this context that we focus on cellular bioenergetics and propose that mitochondria, bioenergetic and signalling organelles, may represent a key cellular target underlying developmental programming. In this review, we discuss empirical findings in animals and humans that suggest that key structural and functional features of mitochondrial biology exhibit developmental plasticity, and are influenced by the same physiological pathways that are implicated in susceptibility for complex, common age-related disorders, and that these targets of mitochondrial developmental programming exhibit long-term temporal stability. We conclude by articulating current knowledge gaps and propose future research directions to bridge these gaps.
健康与疾病发育编程现象背后机制的研究主要集中在特定于感兴趣细胞类型、器官和表型的过程上。然而，观察到暴露于次优或不利发育条件会影响广泛的表型，这表明这些暴露可能还通过在不同细胞和组织类型中共同或共享的细胞机制发挥作用。正是在这种情况下，我们关注细胞生物能量学，并提出线粒体、生物能量和信号细胞器可能是发育编程的关键细胞靶点。在这篇综述中，我们讨论了动物和人类中的经验发现，这些发现表明线粒体生物学的关键结构和功能特征表现出发育可塑性，并受到与复杂、常见与年龄相关疾病易感性相关的相同生理途径的影响，并且这些线粒体发育编程的靶点表现出长期的时间稳定性。我们最后阐明了当前的知识差距，并提出了未来的研究方向来弥合这些差距。
