Changes in mitochondrial homeostasis and redox status in astronauts following long stays in space

Abstract

The effects of long-term exposure to extreme space conditions on astronauts were investigated by analyzing hair samples from ten astronauts who had spent six months on the International Space Station (ISS). Two samples were collected before, during and after their stays in the ISS; hereafter, referred to as Preflight, Inflight and Postflight, respectively. The ratios of mitochondrial (mt) to nuclear (n) DNA and mtRNA to nRNA were analyzed via quantitative PCR. The combined data of Preflight, Inflight and Postflight show a significant reduction in the mtDNA/nDNA in Inflight, and significant reductions in the mtRNA/nRNA ratios in both the Inflight and Postflight samples. The mtRNA/mtDNA ratios were relatively constant, except in the Postflight samples. Using the same samples, the expression of redox and signal transduction related genes, MnSOD, CuZnSOD, Nrf2, Keap1, GPx4 and Catalase was also examined. The results of the combined data from Preflight, Inflight and Postflight show a significant decrease in the expression of all of the redox-related genes in the samples collected Postflight, with the exception of Catalase, which show no change. This decreased expression may contribute to increased oxidative stress Inflight resulting in the mitochondrial damage that is apparent Postflight.

Effects of Iron Overload and Oxidative Damage on the Musculoskeletal System in the Space Environment: Data from Spaceflights and Ground-Based Simulation Models

“…The attenuated antioxidant defense is a possible mechanism for the elevated levels of oxidative stress after flight. Antioxidant gene expression, including Mn superoxide dismutase (Mn–SOD), Cu–Zn–SOD, kelch-like ECH-associated protein 1 (KEAP1), glutathione peroxidase 4 ( GPX4 ), and the regulator of nuclear factor erythroid 2-related factor 2 (NRF2), were significantly decreased in two hair samples from two spacemen who had flown six months on the ISS [ 51 ]. A study assessed the oxidative stress status in 12 Russian cosmonauts, the results exhibited increased granulocyte nitric oxide production and superoxide, increased superoxide dismutase (SOD) activity and glutathione (GSH) oxidation in erythrocyte, and strongly reduced plasma/leucocyte lipophilic antioxidant levels [ 52 ].…”

Redox Signaling and Its Impact on Skeletal and Vascular Responses to Spaceflight

“…The downregulation of antioxidant defenses as a potential mechanism for the increased levels of oxidative damage post-flight is supported by the observation that hair follicle samples from International Space Station (ISS) crew members at post-flight display decreased expression of endogenous antioxidant genes, including Mn superoxide dismutase (MnSOD), CuZnSOD, glutathione peroxidase 4 ( GPX4 ) and kelch-like ECH-associated protein 1 ( KEAP1 ), the regulator of nuclear factor erythroid 2-related factor 2 ( NFE2L2 a.k.a. NRF2 ), a master transcription factor that regulates hundreds of oxidative defense-related genes [ 24 ].…”

“…In the following section, we summarize the state of knowledge on the role of endogenous antioxidant proteins in maintaining skeletal and vascular health with an emphasis on studies using genetic models of gain or loss of protein function. The cytoprotective effect of these proteins on Earth has, therefore, formed the rationale for investigating their importance in tissue and cellular defenses against the stressors associated with spaceflight [ 18 , 24 ] and its Earth-based analogs [ 34 , 35 ]. In this section, we also cite studies that illustrate the emerging role of these antioxidant proteins in modulating skeletal and vascular responses to spaceflight.…”

“…SOD1 gene expression is downregulated in hair follicles of spacefight crew members [ 24 ] while its protein levels are decreased in livers of spaceflown rats [ 18 ] although its role in protecting vasculature and bone from spaceflight stressors needs to be further elucidated. SOD s are the major antioxidant defense systems against O 2 − , catalyzing the conversion of O 2 − to H 2 O 2 , which is then further reduced to water by catalase, peroxiredoxins (PRx), or glutathione peroxidases ( GPX ) [ 64 ].…”

Mitophagy contributes to endothelial adaptation to simulated microgravity

“…On the contrary, rat cardiomyocytes cultured in the RWV upregulated mitochondrial proteins to maintain the energetics of the cells at the expense of protein synthesis, 45 and oligodendrocytes, the myelin-forming cells in the central nervous system, increased mitochondrial respiration in simulated microgravity, suggesting an increase in Kreb's cycle flux. 48 In contrast, within the "NASA Twin Study," higher levels of mtDNA were revealed in peripheral blood mononuclear cells after 1 y in space. 47 Therefore, it is feasible to propose that, while ECs, which are quiescent in normal conditions, can reduce their mitochondria without detrimental effects on their viability, other highly differentiated cells optimize their energetics to meet the challenge generated by gravitational unloading.…”