Division of Exercise Nutrition and Metabolism, Faculty of Sport Sciences, Hacettepe University, Ankara, Turkey.
Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia.
J Physiol. 2024 Feb;602(4):545-568. doi: 10.1113/JP283214. Epub 2024 Jan 9.
Exercise is a powerful non-pharmacological intervention for the treatment and prevention of numerous chronic diseases. Contracting skeletal muscles provoke widespread perturbations in numerous cells, tissues and organs, which stimulate multiple integrated adaptations that ultimately contribute to the many health benefits associated with regular exercise. Despite much research, the molecular mechanisms driving such changes are not completely resolved. Technological advancements beginning in the early 1960s have opened new avenues to explore the mechanisms responsible for the many beneficial adaptations to exercise. This has led to increased research into the role of small peptides (<100 amino acids) and mitochondrially derived peptides in metabolism and disease, including those coded within small open reading frames (sORFs; coding sequences that encode small peptides). Recently, it has been hypothesized that sORF-encoded mitochondrially derived peptides and other small peptides play significant roles as exercise-sensitive peptides in exercise-induced physiological adaptation. In this review, we highlight the discovery of mitochondrially derived peptides and newly discovered small peptides involved in metabolism, with a specific emphasis on their functions in exercise-induced adaptations and the prevention of metabolic diseases. In light of the few studies available, we also present data on how both single exercise sessions and exercise training affect expression of sORF-encoded mitochondrially derived peptides. Finally, we outline numerous research questions that await investigation regarding the roles of mitochondrially derived peptides in metabolism and prevention of various diseases, in addition to their roles in exercise-induced physiological adaptations, for future studies.
运动是治疗和预防许多慢性疾病的一种强有力的非药物干预手段。收缩的骨骼肌会引起许多细胞、组织和器官的广泛扰动，这些扰动刺激了多种综合适应，最终有助于经常运动带来的许多健康益处。尽管进行了大量研究，但驱动这些变化的分子机制仍未完全解决。20 世纪 60 年代初开始的技术进步为探索运动适应的许多有益机制开辟了新途径。这导致人们对小肽（<100 个氨基酸）和线粒体衍生肽在代谢和疾病中的作用的研究增加，包括那些在小开放阅读框（sORF；编码小肽的编码序列）中编码的肽。最近，有人假设 sORF 编码的线粒体衍生肽和其他小肽在运动引起的生理适应中作为运动敏感肽发挥重要作用。在这篇综述中，我们重点介绍了与代谢有关的线粒体衍生肽和新发现的小肽的发现，特别强调了它们在运动诱导的适应和代谢性疾病预防中的功能。鉴于目前可用的研究较少，我们还介绍了单次运动和运动训练如何影响 sORF 编码的线粒体衍生肽表达的数据。最后，我们概述了许多关于线粒体衍生肽在代谢和预防各种疾病中的作用以及它们在运动诱导的生理适应中的作用的研究问题，以供未来的研究。
