Department of Cell Biology, Blavatnik Institute, Ludwig Center, Harvard Medical School, Boston, MA 02115, USA.
Federal University of São Paulo, Department of Gynecology, Rua Napoleão de Barros 632, 04024-002, Vila Clementino, São Paulo, SP, Brazil.
Ageing Res Rev. 2021 Sep;70:101378. doi: 10.1016/j.arr.2021.101378. Epub 2021 Jun 4.
The oocyte is recognised as the largest cell in mammalian species and other multicellular organisms. Mitochondria represent a high proportion of the cytoplasm in oocytes and mitochondrial architecture is different in oocytes than in somatic cells, characterised by a rounder appearance and fragmented network. Although the number of mitochondria per oocyte is higher than in any other mammalian cell, their number and activity decrease with advancing age. Mitochondria integrate numerous processes essential for cellular function, such as metabolic processes related to energy production, biosynthesis, and waste removal, as well as Ca signalling and reactive oxygen species (ROS) homeostasis. Further, mitochondria are responsible for the cellular adaptation to different types of stressors such as oxidative stress or DNA damage. When these stressors outstrip the adaptive capacity of mitochondria to restore homeostasis, it leads to mitochondrial dysfunction. Decades of studies indicate that mitochondrial function is multifaceted, which is reflected in the oocyte, where mitochondria support numerous processes during oocyte maturation, fertilization, and early embryonic development. Dysregulation of mitochondrial processes has been consistently reported in ageing and age-related diseases. In this review, we describe the functions of mitochondria as bioenergetic powerhouses and signal transducers in oocytes, how dysfunction of mitochondrial processes contributes to reproductive ageing, and whether mitochondria could be targeted to promote oocyte rejuvenation.
卵母细胞被认为是哺乳动物和其他多细胞生物中最大的细胞。线粒体在卵母细胞的细胞质中占有很大比例,其结构与体细胞不同,表现为更圆的形态和碎片化的网络。尽管每个卵母细胞中的线粒体数量高于任何其他哺乳动物细胞,但随着年龄的增长,其数量和活性会下降。线粒体整合了许多对细胞功能至关重要的过程,例如与能量产生、生物合成和废物清除相关的代谢过程,以及 Ca 信号和活性氧 (ROS) 稳态。此外,线粒体负责细胞对不同类型应激源的适应,如氧化应激或 DNA 损伤。当这些应激源超过线粒体恢复内稳态的适应能力时,就会导致线粒体功能障碍。数十年来的研究表明,线粒体功能是多方面的,这反映在卵母细胞中,线粒体在卵母细胞成熟、受精和早期胚胎发育过程中支持许多过程。线粒体过程的失调在衰老和与年龄相关的疾病中一直被报道。在这篇综述中,我们描述了线粒体作为生物能工厂和信号转导器在卵母细胞中的功能,线粒体过程的功能障碍如何导致生殖衰老,以及线粒体是否可以作为靶点来促进卵母细胞的年轻化。