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      The mitochondrial proteomic changes of rat hippocampus induced by 28-day simulated microgravity

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          Abstract

          A large number of aerospace practices have confirmed that the aerospace microgravity environment can lead to cognitive function decline. Mitochondria are the most important energy metabolism organelles, and some studies demonstrate that the areospace microgravity environment can cause mitochondrial dysfunction. However, the relationships between cognitive function decline and mitochondrial dysfunction in the microgravity environment have not been elucidated. In this study, we simulated the microgravity environment in the Sprague-Dawley (SD) rats by -30° tail suspension for 28 days. We then investigated the changes of mitochondrial morphology and proteomics in the hippocampus. The electron microscopy results showed that the 28-day tail suspension increased the mitochondria number and size of rat hippocampal neuronal soma. Using TMT-based proteomics analysis, we identified 163 differentially expressed proteins (DEPs) between tail suspension and control samples, and among them, 128 proteins were upregulated and 35 proteins were downregulated. Functional and network analyses of the DEPs indicated that several of mitochondrial metabolic processes including the tricarboxylic acid (TCA) cycle were altered by simulating microgravity (SM). We verified 3 upregulated proteins, aconitate hydratase (ACO2), dihydrolipoamide S-succinyltransferase (DLST), and citrate synthase (CS), in the TCA cycle process by western blotting and confirmed their differential expressions between tail suspension and control samples. Taken together, our results demonstrate that 28-day tail suspension can cause changes in the morphology and metabolic function of hippocampus mitochondria, which might represent a mechanism of cognitive disorder caused by aerospace microgravity.

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          The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight.

          To understand the health impact of long-duration spaceflight, one identical twin astronaut was monitored before, during, and after a 1-year mission onboard the International Space Station; his twin served as a genetically matched ground control. Longitudinal assessments identified spaceflight-specific changes, including decreased body mass, telomere elongation, genome instability, carotid artery distension and increased intima-media thickness, altered ocular structure, transcriptional and metabolic changes, DNA methylation changes in immune and oxidative stress-related pathways, gastrointestinal microbiota alterations, and some cognitive decline postflight. Although average telomere length, global gene expression, and microbiome changes returned to near preflight levels within 6 months after return to Earth, increased numbers of short telomeres were observed and expression of some genes was still disrupted. These multiomic, molecular, physiological, and behavioral datasets provide a valuable roadmap of the putative health risks for future human spaceflight.
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            Mitochondria and Mitochondrial Cascades in Alzheimer’s Disease

            Decades of research indicate mitochondria from Alzheimer’s disease (AD) patients differ from those of non-AD individuals. Initial studies revealed structural differences, and subsequent studies showed functional deficits. Observations of structure and function changes prompted investigators to consider the consequences, significance, and causes of AD-related mitochondrial dysfunction. Currently, extensive research argues mitochondria may mediate, drive, or contribute to a variety of AD pathologies. The perceived significance of these mitochondrial changes continues to grow, and many currently believe AD mitochondrial dysfunction represents a reasonable therapeutic target. Debate continues over the origin of AD mitochondrial changes. Some argue amyloid-β (Aβ) induces AD mitochondrial dysfunction, a view that does not challenge the amyloid cascade hypothesis and that may in fact help explain that hypothesis. Alternatively, data indicate mitochondrial dysfunction exists independent of Aβ, potentially lies upstream of Aβ deposition, and suggest a primary mitochondrial cascade hypothesis that assumes mitochondrial pathology hierarchically supersedes Aβ pathology. Mitochondria, therefore, appear at least to mediate or possibly even initiate pathologic molecular cascades in AD. This review considers studies and data that inform this area of AD research.
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              Mitochondria in Health and Disease

              Mitochondria are best known as the sites for production of respiratory ATP and are essential for eukaryotic life. They have their own genome but the great majority of the mitochondrial proteins are encoded by the nuclear genome and are imported into the mitochondria. The mitochondria participate in critical central metabolic pathways and they are fully integrated into the intracellular signalling networks that regulate diverse cellular functions. It is not surprising then that mitochondrial defects or dysregulation have emerged as having key roles in ageing and in the cytopathological mechanisms underlying cancer, neurodegenerative and other diseases. This special issue contains 12 publications—nine review articles and three original research articles. They cover diverse areas of mitochondrial biology and function and how defects in these areas can lead to disease. In addition, the articles in this issue highlight how model organisms have contributed to our understanding of these processes.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: Data curationRole: InvestigationRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: Investigation
                Role: Investigation
                Role: Investigation
                Role: MethodologyRole: Writing – review & editing
                Role: Funding acquisitionRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                10 March 2022
                2022
                : 17
                : 3
                : e0265108
                Affiliations
                [1 ] State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
                [2 ] Department of Pathology and Forensics, College of Basic Medical Sciences, Dalian Medical University, Dalian, China
                Universita degli studi della Campania, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0001-6023-2258
                Article
                PONE-D-21-31461
                10.1371/journal.pone.0265108
                8912132
                35271667
                c2ff2c8c-aad4-4421-881b-44bfa6505950
                © 2022 Ji et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 September 2021
                : 23 February 2022
                Page count
                Figures: 4, Tables: 5, Pages: 18
                Funding
                Funded by: The Foundation of State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center
                Award ID: SMFA17A03, SMFA19B02, SMFA19K08
                Award Recipient :
                Funded by: The National Natural Science Foundation of China
                Award ID: 21635001, 31800707, 31800998
                Award Recipient :
                This work was supported by The Foundation of State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center (SMFA17A03, SMFA19B02, SMFA19K08, SMFA20A01), The National Natural Science Foundation of China (21635001, 31800707, 31800998). The funders had no role in the study design, data collection and analysis, decision to publish, and preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Biochemistry
                Bioenergetics
                Energy-Producing Organelles
                Mitochondria
                Biology and Life Sciences
                Cell Biology
                Cellular Structures and Organelles
                Energy-Producing Organelles
                Mitochondria
                Biology and Life Sciences
                Anatomy
                Brain
                Hippocampus
                Medicine and Health Sciences
                Anatomy
                Brain
                Hippocampus
                Biology and Life Sciences
                Biochemistry
                Enzymology
                Enzymes
                Oxidoreductases
                Dehydrogenases
                Biology and Life Sciences
                Biochemistry
                Proteins
                Enzymes
                Oxidoreductases
                Dehydrogenases
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Metabolic Pathways
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Protein Metabolism
                Biology and Life Sciences
                Biochemistry
                Proteins
                Serum Proteins
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Metabolic Processes
                Citric Acid Cycle
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Energy Metabolism
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Energy Metabolism
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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