Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact.

Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration.

Mitochondria are considered as the power‐generating units of the cell due to their key role in energy metabolism and cell signaling. However, mitochondrial components could be found in the extracellular space, as fragments or encapsulated in vesicles. In addition, this intact organelle has been recently reported to be released by platelets exclusively in specific conditions. Here, we demonstrate for the first time, that blood preparation with resting platelets, contains whole functional mitochondria in normal physiological state. Likewise, we show, that normal and tumor cultured cells are able to secrete their mitochondria. Using serial centrifugation or filtration followed by polymerase chain reaction‐based methods, and Whole Genome Sequencing, we detect extracellular full‐length mitochondrial DNA in particles over 0.22 µm holding specific mitochondrial membrane proteins. We identify these particles as intact cell‐free mitochondria using fluorescence‐activated cell sorting analysis, fluorescence microscopy, and transmission electron microscopy. Oxygen consumption analysis revealed that these mitochondria are respiratory competent. In view of previously described mitochondrial potential in intercellular transfer, this discovery could greatly widen the scope of cell‐cell communication biology. Further steps should be developed to investigate the potential role of mitochondria as a signaling organelle outside the cell and to determine whether these circulating units could be relevant for early detection and prognosis of various diseases.

Blood contains circulating cell free respiratory competent mitochondria / Blood contains circulating cell free respiratory competent mitochondria: Blood contains extracellular mitochondria

Abstract Bone remodeling is a lifelong process that gives rise to a mature, dynamic bone structure via a balance between bone formation by osteoblasts and resorption by osteoclasts. These opposite processes allow the accommodation of bones to dynamic mechanical forces, altering bone mass in response to changing conditions. Mechanical forces are indispensable for bone homeostasis; skeletal formation, resorption, and adaptation are dependent on mechanical signals, and loss of mechanical stimulation can therefore significantly weaken the bone structure, causing disuse osteoporosis and increasing the risk of fracture. The exact mechanisms by which the body senses and transduces mechanical forces to regulate bone remodeling have long been an active area of study among researchers and clinicians. Such research will lead to a deeper understanding of bone disorders and identify new strategies for skeletal rejuvenation. Here, we will discuss the mechanical properties, mechanosensitive cell populations, and mechanotransducive signaling pathways of the skeletal system. 

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Mechanical regulation of bone remodeling

Circulating miRNA Spaceflight Signature Reveals Targets for Countermeasure Development.

Cell-free DNA (cfDNA) and Exosome Profiling from a Year-Long Human Spaceflight Reveals Circulating Biomarkers.

To better understand the effects of long-term spaceflight on the human body, the NASA Twins Study was initiated as the first multi-omic, molecular, physiological, and behavioral profile of astronauts, during NASA’s first one-year mission on the International Space Station. The biochemical profile expressed upon landing showed significant increases in markers associated with initiation or resolution of inflammation as well as skeletal muscle regeneration : interleukin-6 (IL-6), C-reactive protein (CRP), interleukin-10 (IL-10), C-C motif chemokine ligand 2 (CCL2/MCP1), and interleukin-1 receptor antagonist (IL-1ra).  These results were supported by single-cell gene expression and epitope (scAbSeq) analysis of peripheral blood monocytes (PBMCs), which showed changes to composition and expression consistent with flight-induced cytokine changes. Moreover, a simultaneous  decrease was seen in markers that had been elevated during flight, including tumor necrosis factor α (TNFα), interleukin-1α (IL-1α) and interleukin-1β (IL-1β) among others, markers which are typically associated with bone metabolism and early stages of muscle regeneration. The changes observed in these markers are suggestive of skeletal muscle response to gravity as it transitions from a state of weightlessness and atrophy to load-bearing conditions and regeneration.  Since this transition often leads to pain and inflammation, we examine here potential pharmacological manipulations as a means to ameliorate discomfort upon landing, which can provide guidance for future missions.

Chris Mozsary

Papers

Cell-free DNA (cfDNA) and Exosome Profiling from a Year-Long Human Spaceflight Reveals Circulating Biomarkers.

Multi-Omic, Single-Cell, and Biochemical Profiles of Astronauts Guide Pharmacological Strategies for Returning to Gravity