An evolutionary, or "Mitocentric" perspective on cellular function and disease
An evolutionary, or "Mitocentric" perspective on cellular function and disease
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DOI：
10.1016/j.redox.2020.101568
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发表时间：
2020-09-01
期刊：
影响因子：
11.4
通讯作者：
Ballinger, Scott W.
中科院分区：
文献类型：
--
作者：
Brown, Jamelle A.;Sammy, Melissa J.;Ballinger, Scott W.
具有复杂遗传病因的常见代谢性疾病（例如肥胖症、心血管疾病、糖尿病）的发病率在全国和全球范围内稳步上升。虽然几十年来一直在寻找解释这些疾病易感性和风险的遗传模型，但尚未发现明确的范式来解开多基因/复杂疾病发展的遗传基础。由于真核细胞的进化涉及到细胞核和细胞核（它本身是一个遗传杂种）的前身之间的共生相互作用，我们认为，这一历史提供了一个合理的基础，调查是否遗传相互作用和共同进化的这些基因组仍然存在。我们认为线粒体和孟德尔遗传学或“线粒体-孟德尔”遗传学在细胞功能中起着重要作用，从而影响疾病风险。该范例考虑了线粒体和核DNA背景在本文讨论的多种线粒体功能上的自然变化和共同进化，包括能量产生、细胞信号传导和免疫应答，其共同地可以影响疾病发展。在这些过程的关系是线粒体代谢的经济，由线粒体和核基因组编程。
The incidence of common, metabolic diseases (e.g. obesity, cardiovascular disease, diabetes) with complex genetic etiology has been steadily increasing nationally and globally. While identification of a genetic model that explains susceptibility and risk for these diseases has been pursued over several decades, no clear paradigm has yet been found to disentangle the genetic basis of polygenic/complex disease development. Since the evolution of the eukaryotic cell involved a symbiotic interaction between the antecedents of the mitochondrion and nucleus (which itself is a genetic hybrid), we suggest that this history provides a rational basis for investigating whether genetic interaction and co-evolution of these genomes still exists. We propose that both mitochondrial and Mendelian, or "mito-Mendelian" genetics play a significant role in cell function, and thus disease risk. This paradigm contemplates the natural variation and co-evolution of both mitochondrial and nuclear DNA backgrounds on multiple mitochondrial functions that are discussed herein, including energy production, cell signaling and immune response, which collectively can influence disease development. At the nexus of these processes is the economy of mitochondrial metabolism, programmed by both mitochondrial and nuclear genomes.