Spaceflight Activates Autophagy Programs and the Proteasome in Mouse Liver

• Published in: International journal of molecular sciences Vol. 18; no. 10; p. 2062
• Main Authors: Blaber, Elizabeth A., Pecaut, Michael J., Jonscher, Karen R.
• Format: Journal Article
• Language: English
• Published: Ames Research Center MDPI 27-09-2017; MDPI AG
• Subjects: Aberration; Aerospace environments; Aerospace Medicine; Animals; Atlantis (orbiter); Autophagy; Betaine - metabolism; Biosynthesis; Cellular Senescence; Cluster Analysis; Dehydration; Enrichment; Female; Gene Expression Profiling; Glutathione - metabolism; Lipid Metabolism; Liver; Liver - metabolism; Liver - pathology; Metabolic Networks and Pathways; Metabolic pathways; Metabolism; Metabolome; Metabolomics; Metabolomics - methods; Mice; Mitochondria; Oxidation-Reduction; Oxidative Stress; Phagocytosis; Post-translation; Proteases; proteasome; Proteasome Endopeptidase Complex - metabolism; Proteasomes; Protein Biosynthesis; RNA, Transfer - biosynthesis; Rodents; Senescence; Space exploration; Space Flight; spaceflight; Studies; Transcriptome; tRNA; tRNA biosynthesis; Ubiquitin; Metabolomic; Autophagy; Spaceflight; senescence; proteasome; spaceflight; autophagy; tRNA biosynthesis; metabolomics
• ISSN: 1661-6596; 1422-0067; 1422-0067
• DOI: 10.3390/ijms18102062

Increased oxidative stress is an unavoidable consequence of exposure to the space environment. Our previous studies showed that mice exposed to space for 13.5 days had decreased glutathione levels, suggesting impairments in oxidative defense. Here we performed unbiased, unsupervised and integrated multi-'omic analysis of metabolomic and transcriptomic datasets from mice flown aboard the Space Shuttle Atlantis. Enrichment analyses of metabolite and gene sets showed significant changes in osmolyte concentrations and pathways related to glycerophospholipid and sphingolipid metabolism, likely consequences of relative dehydration of the spaceflight mice. However, we also found increased enrichment of aminoacyl-tRNA biosynthesis and purine metabolic pathways, concomitant with enrichment of genes associated with autophagy and the ubiquitin-proteasome. When taken together with a down-regulation in NRF2-mediated signaling, our analyses suggest that decreased hepatic oxidative defense may lead to aberrant tRNA post-translational processing, induction of degradation programs and senescence-associated mitochondrial dysfunction in response to the spaceflight environment..