Department of Cell Biology and Anatomy, New York Medical College, 15 Dana Road, Valhalla, NY, U.S.A.
Biochem Soc Trans. 2023 Apr 26;51(2):501-512. doi: 10.1042/BST20220616.
Protein homeostasis (proteostasis) is essential for cellular function and organismal health and requires the concerted actions of protein synthesis, folding, transport, and turnover. In sexually reproducing organisms, the immortal germline lineage passes genetic information across generations. Accumulating evidence indicates the importance of proteome integrity for germ cells as genome stability. As gametogenesis involves very active protein synthesis and is highly energy-demanding, it has unique requirements for proteostasis regulation and is sensitive to stress and nutrient availability. The heat shock factor 1 (HSF1), a key transcriptional regulator of cellular response to cytosolic and nuclear protein misfolding has evolutionarily conserved roles in germline development. Similarly, insulin/insulin-like growth factor-1 (IGF-1) signaling, a major nutrient-sensing pathway, impacts many aspects of gametogenesis. Here, we focus on HSF1 and IIS to review insights into their roles in germline proteostasis and discuss the implications on gamete quality control during stress and aging.
蛋白质动态平衡(稳态)对于细胞功能和生物体健康至关重要,需要蛋白质合成、折叠、运输和周转的协同作用。在有性繁殖的生物体中,不朽的生殖系通过遗传信息在代际之间传递。越来越多的证据表明,蛋白质组完整性对于生殖细胞作为基因组稳定性非常重要。由于配子发生涉及非常活跃的蛋白质合成并且对能量需求很高,因此它对蛋白质动态平衡的调节具有独特的要求,并且对压力和营养可用性敏感。热休克因子 1(HSF1)是细胞对细胞质和核蛋白错误折叠反应的关键转录调节剂,在生殖系发育中具有进化保守的作用。同样,胰岛素/胰岛素样生长因子-1(IGF-1)信号通路是一种主要的营养感应途径,影响配子发生的许多方面。在这里,我们专注于 HSF1 和 IIS,以综述它们在生殖系蛋白质动态平衡中的作用的见解,并讨论在压力和衰老期间对配子质量控制的影响。