A.N. Belozersky Research Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
Department of Reproduction Management, Leibniz-Institute for Zoo and Wildlife Research, Alfred-Kowalke-Str. 17, 10315 Berlin, Germany.
Int J Mol Sci. 2022 Aug 13;23(16):9067. doi: 10.3390/ijms23169067.
The reason for the exceptional longevity of the naked mole rat () remains a mystery to researchers. We assumed that evolutionarily, acquired the ability to quickly stabilize the functioning of mitochondria and endoplasmic reticulum (ER) to adjust metabolism to external challenges. To test this, a comparison of the hepatic mitochondria and ER of and C57BL/6 mice was done. Electron microscopy showed that 2-months-old mice have more developed rough ER (RER) than smooth ER (SER), occupying ~17 and 2.5% of the hepatocytic area correspondingly, and these values do not change with age. On the other hand, in 1-week-old , RER occupies only 13% constantly decreasing with age, while SER occupies 35% in a 1-week-old animal, constantly rising with age. The different localization of mitochondria in and mouse hepatocytes was confirmed by confocal and electron microscopy: while in mitochondria were mainly clustered around the nucleus and on the periphery of the cell, in mouse hepatocytes they were evenly distributed throughout the cell. We suggest that the noted structural and spatial features of ER and mitochondria in reflect adaptive rearrangements aimed at greater tolerance of the cellular system to challenges, primarily hypoxia and endogenous and exogenous toxins. Different mechanisms of adaptive changes including an activated hepatic detoxification system as a hormetic response, are discussed considering the specific metabolic features of the naked mole rat.
裸鼹鼠()异常长寿的原因仍然是研究人员的一个谜。我们假设,从进化的角度来看,它获得了快速稳定线粒体和内质网(ER)功能的能力,以调整新陈代谢以应对外部挑战。为了验证这一点,对裸鼹鼠和 C57BL/6 小鼠的肝线粒体和 ER 进行了比较。电子显微镜显示,2 个月大的裸鼹鼠的粗面内质网(RER)比光滑内质网(SER)发育更为成熟,分别占肝细胞面积的~17%和 2.5%,且这些值不随年龄变化而变化。另一方面,在 1 周大的裸鼹鼠中,RER 始终仅占 13%,并随年龄不断减少,而 SER 则在 1 周大的动物中占 35%,并随年龄不断增加。通过共聚焦和电子显微镜证实了裸鼹鼠和小鼠肝细胞中线粒体的不同定位:在裸鼹鼠中,线粒体主要聚集在细胞核周围和细胞外围,而在小鼠肝细胞中,线粒体均匀分布在整个细胞中。我们认为,ER 和线粒体在裸鼹鼠中的这些明显的结构和空间特征反映了适应重排,旨在提高细胞系统对挑战(主要是缺氧以及内源性和外源性毒素)的耐受性。考虑到裸鼹鼠的特定代谢特征,讨论了包括激活肝解毒系统在内的不同适应变化机制,将其视为一种应激反应。