Considerable progress has been made in understanding the physiological basis for variation in the life-history patterns of animals, particularly with regard to the roles of oxidative stress and hormonal regulation. However, an underappreciated and understudied area that could play a role in mediating inter- and intraspecific variation of life history is endoplasmic reticulum (ER) stress, and the resulting unfolded protein response (UPRER ). ER stress response and the UPRER maintain proteostasis in cells by reducing the intracellular load of secretory proteins and enhancing protein folding capacity or initiating apoptosis in cells that cannot recover. Proper modulation of the ER stress response and execution of the UPRER allow animals to respond to intracellular and extracellular stressors and adapt to constantly changing environments. ER stress responses are heritable and there is considerable individual variation in UPRER phenotype in animals, suggesting that ER stress and UPRER phenotype can be subjected to natural selection. The variation in UPRER phenotype presumably reflects the way animals respond to ER stress and environmental challenges. Most of what we know about ER stress and the UPRER in animals has either come from biomedical studies using cell culture or from experiments involving conventional laboratory or agriculturally important models that exhibit limited genetic diversity. Furthermore, these studies involve the assessment of experimentally induced qualitative changes in gene expression as opposed to the quantitative variations that occur in naturally existing populations. Almost all of these studies were conducted in controlled settings that are often quite different from the conditions animals experience in nature. Herein, we review studies that investigated ER stress and the UPRER in relation to key life-history traits including growth and development, reproduction, bioenergetics and physical performance, and ageing and senescence. We then ask if these studies can inform us about the role of ER stress and the UPRER in mediating the aforementioned life-history traits in free-living animals. We propose that there is a need to conduct experiments pertaining to ER stress and the UPRER in ecologically relevant settings, to characterize variation in ER stress and the UPRER in free-living animals, and to relate the observed variation to key life-history traits. We urge others to integrate multiple physiological systems and investigate how interactions between ER stress and oxidative stress shape life-history trade-offs in free-living animals.

中文翻译：

---

从生态学和进化的角度评估内质网应激和未折叠蛋白反应

在了解动物生活史模式变化的生理基础方面取得了相当大的进展，特别是在氧化应激和激素调节的作用方面。然而，一个被低估和研究不足的领域是内质网（ER）应激和由此产生的未折叠蛋白反应（UPRER），它可能在介导生活史的种间和种内变异中发挥作用。ER 应激反应和 UPRER 通过减少分泌蛋白的细胞内负荷和增强蛋白质折叠能力或在无法恢复的细胞中启动细胞凋亡来维持细胞中的蛋白质稳态。ER 应激反应的适当调节和 UPRER 的执行使动物能够对细胞内和细胞外应激源作出反应，并适应不断变化的环境。ER 应激反应是可遗传的，动物的 UPRER 表型存在相当大的个体差异，这表明 ER 应激和 UPRER 表型可以接受自然选择。UPRER 表型的变化可能反映了动物对 ER 压力和环境挑战的反应方式。我们对动物内质网应激和 UPRER 的大部分了解要么来自使用细胞培养的生物医学研究，要么来自涉及传统实验室或具有有限遗传多样性的农业重要模型的实验。此外，这些研究涉及评估实验诱导的基因表达的质量变化，而不是自然存在的种群中发生的数量变化。几乎所有这些研究都是在受控环境中进行的，这些环境通常与动物在自然界中经历的条件截然不同。在此，我们回顾了研究 ER 压力和 UPRER 与关键生命史特征相关的研究，这些特征包括生长和发育、繁殖、生物能量学和身体机能以及衰老和衰老。然后我们询问这些研究是否可以让我们了解 ER 压力和 UPRER 在调节自由生活动物的上述生活史特征中的作用。我们建议有必要在生态相关环境中进行与 ER 应激和 UPRER 有关的实验，以表征自由生活动物中 ER 应激和 UPRER 的变化，并将观察到的变化与关键的生活史特征联系起来。