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Mitochondrial-derived peptides and exercise
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 2.8 ) Pub Date : 2021-09-11 , DOI: 10.1016/j.bbagen.2021.130011
Jonathan S T Woodhead 1 , Troy L Merry 1
Affiliation  

Acute exercise, and in particular aerobic exercise, increases skeletal muscle energy demand causing mitochondrial stress, and mitochondrial-related adaptations which are a hallmark of exercise training. Given that mitochondria are central players in the exercise response, it is imperative that they have networks that can communicate their status both intra- and inter-cellularly. Peptides encoded by short open-reading frames within mitochondrial DNA, mitochondrial-derived peptides (MDPs), have been suggested to form a newly recognised branch of this retrograde signalling cascade that contribute to coordinating the adaptive response to regular exercise. Here we summarise the recent evidence that acute high intensity exercise in humans can increase concentrations of the MDPs humanin and MOTS-c in skeletal muscle and plasma, and speculate on the mechanisms controlling MDP responses to exercise stress. Evidence that exercise training results in chronic changes in MDP expression within tissues and the circulation is conflicting and may depend on the mode, duration, intensity of training plan and participant characteristics. Further research is required to define the effect of these variables on MDPs and to determine whether MDPs other than MOTS-c have exercise mimetic properties. MOTS-c treatment of young and aged mice improves exercise capacity/performance and leads to adaptions that are similar to that of being physically active (weight loss, increased antioxidant capacity and improved insulin sensitivity), however, studies utilising a MOTS-c inactivating genetic variant or combination of exercise + MOTS-c treatment in mice suggest that there are distinct and overlapping pathways through which exercise and MOTS-c evoke metabolic benefits. Overall, MOTS-c, and potentially other MDPs, may be exercise-sensitive myokines and further work is required to define inter- and intra-tissue targets in an exercise context.



中文翻译:


线粒体衍生肽与运动



剧烈运动,特别是有氧运动,会增加骨骼肌能量需求,导致线粒体应激和线粒体相关适应,这是运动训练的标志。鉴于线粒体是运动反应的核心参与者,它们必须拥有能够在细胞内和细胞间传达其状态的网络。由线粒体 DNA 内的短开放阅读框编码的肽,即线粒体衍生肽 (MDP),已被认为形成了这种逆行信号级联的一个新认识的分支,有助于协调对定期运动的适应性反应。在这里,我们总结了最近的证据,表明人类急性高强度运动可以增加骨骼肌和血浆中 MDP 护脑素和 MOTS-c 的浓度,并推测控制 MDP 对运动应激反应的机制。运动训练导致组织和循环内 MDP 表达慢性变化的证据是相互矛盾的,可能取决于训练计划的模式、持续时间、强度和参与者特征。需要进一步的研究来定义这些变量对 MDP 的影响,并确定除 MOTS-c 之外的 MDP 是否具有运动模拟特性。 MOTS-c 治疗年轻和老年小鼠可提高运动能力/表现,并导致类似于体力活动的适应(体重减轻、抗氧化能力增强和胰岛素敏感性提高),然而,利用 MOTS-c 失活基因的研究运动 + MOTS-c 治疗小鼠的变体或组合表明,运动和 MOTS-c 通过不同且重叠的途径产生代谢益处。 总体而言,MOTS-c 和潜在的其他 MDP 可能是运动敏感的肌因子,需要进一步的工作来定义运动背景下的组织间和组织内目标。

更新日期:2021-09-17
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