Murgia Marta, Rittweger Jörn, Reggiani Carlo, Bottinelli Roberto, Mann Matthias, Schiaffino Stefano, Narici Marco V
Department of Biomedical Sciences, University of Padova, 35131, Padua, Italy.
Max-Planck-Institute of Biochemistry, 82152, Martinsried, Germany.
NPJ Microgravity. 2024 Jun 5;10(1):60. doi: 10.1038/s41526-024-00406-3.
Skeletal muscle undergoes atrophy and loss of force during long space missions, when astronauts are persistently exposed to altered gravity and increased ionizing radiation. We previously carried out mass spectrometry-based proteomics from skeletal muscle biopsies of two astronauts, taken before and after a mission on the International Space Station. The experiments were part of an effort to find similarities between spaceflight and bed rest, a ground-based model of unloading, focused on proteins located at the costameres. We here extend the data analysis of the astronaut dataset and show compartment-resolved changes in the mitochondrial proteome, remodeling of the extracellular matrix and of the antioxidant response. The astronauts differed in their level of onboard physical exercise, which correlated with their respective preservation of muscle mass and force at landing in previous analyses. We show that the mitochondrial proteome downregulation during spaceflight, particularly the inner membrane and matrix, was dramatic for both astronauts. The expression of autophagy regulators and reactive oxygen species scavengers, however, showed partially opposite expression trends in the two subjects, possibly correlating with their level of onboard exercise. As mitochondria are primarily affected in many different tissues during spaceflight, we hypothesize that reactive oxygen species (ROS) rather than mechanical unloading per se could be the primary cause of skeletal muscle mitochondrial damage in space. Onboard physical exercise might have a strong direct effect on the prevention of muscle atrophy through mechanotransduction and a subsidiary effect on mitochondrial quality control, possibly through upregulation of autophagy and anti-oxidant responses.
在长期太空任务中，当宇航员持续暴露于重力改变和电离辐射增加的环境时，骨骼肌会发生萎缩并丧失力量。我们之前对两名宇航员在执行国际空间站任务前后进行的骨骼肌活检样本开展了基于质谱的蛋白质组学研究。这些实验是一项旨在寻找太空飞行与卧床休息（一种地面模拟失重的模型）之间相似性的工作的一部分，重点关注位于肌节的蛋白质。我们在此扩展了对宇航员数据集的数据分析，展示了线粒体蛋白质组在不同区室的变化、细胞外基质的重塑以及抗氧化反应。宇航员在太空船上的体育锻炼水平存在差异，在之前的分析中，这与他们着陆时各自肌肉质量和力量的保持情况相关。我们发现，在太空飞行期间，两名宇航员的线粒体蛋白质组均出现显著下调，尤其是线粒体内膜和基质的蛋白质组。然而，自噬调节因子和活性氧清除剂的表达在两名受试者中呈现出部分相反的趋势，这可能与他们在太空船上的锻炼水平有关。由于在太空飞行期间许多不同组织中主要受影响的是线粒体，我们推测活性氧（ROS）而非机械卸载本身可能是太空骨骼肌线粒体损伤的主要原因。太空船上的体育锻炼可能通过机械转导对预防肌肉萎缩产生强大的直接影响，并可能通过上调自噬和抗氧化反应对线粒体质量控制产生辅助作用。
