Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
Physiol Res. 2021 Dec 30;70(Suppl4):S471-S484. doi: 10.33549/physiolres.934740.
Mitochondrial retrograde signaling is a pathway of communication from mitochondria to the nucleus. Recently, natural mitochondrial genome (mtDNA) polymorphisms (haplogroups) received increasing attention in the pathophysiology of human common diseases. However, retrograde effects of mtDNA variants on such traits are difficult to study in humans. The conplastic strains represent key animal models to elucidate regulatory roles of mtDNA haplogroups on defined nuclear genome background. To analyze the relationship between mtDNA variants and cardiometabolic traits, we derived a set of rat conplastic strains (SHR-mtBN, SHR-mtF344 and SHR-mtLEW), harboring all major mtDNA haplotypes present in common inbred strains on the nuclear background of the spontaneously hypertensive rat (SHR). The BN, F344 and LEW mtDNA differ from the SHR in multiple amino acid substitutions in protein coding genes and also in variants of tRNA and rRNA genes. Different mtDNA haplotypes were found to predispose to various sets of cardiometabolic phenotypes which provided evidence for significant retrograde effects of mtDNA in the SHR. In the future, these animals could be used to decipher individual biochemical components involved in the retrograde signaling.
线粒体逆行信号是一种从线粒体到细胞核的通讯途径。最近，天然线粒体基因组（mtDNA）多态性（单倍群）在人类常见疾病的病理生理学中受到越来越多的关注。然而，mtDNA 变异对这些特征的逆行影响在人类中很难研究。嵌合体品系是阐明 mtDNA 单倍群在特定核基因组背景下对定义核基因组的调控作用的关键动物模型。为了分析 mtDNA 变异与心脏代谢特征之间的关系，我们构建了一组大鼠嵌合体品系（SHR-mtBN、SHR-mtF344 和 SHR-mtLEW），这些品系在自发性高血压大鼠（SHR）的核背景下携带了常见近交系中存在的所有主要 mtDNA 单倍型。BN、F344 和 LEW mtDNA 在蛋白质编码基因中的多个氨基酸取代以及 tRNA 和 rRNA 基因的变异方面与 SHR 不同。不同的 mtDNA 单倍型易患各种心脏代谢表型，这为 SHR 中 mtDNA 的显著逆行效应提供了证据。将来，这些动物可以用于破译逆行信号中涉及的个体生化成分。
