Extracellular mitochondrial DNA and extracellular mitochondria as biomarkers of spaceflight stress: implications for safeguarding astronaut health

The detection of extracellular mitochondrial DNA (ex-mtDNA) and extracellular mitochondria (ex-Mito) in astronauts’ blood during space missions raises intriguing questions about their potential roles in human health under the unique stressors of spaceflight. However, current methods for detecting ex-mtDNA and ex-Mito in blood samples collected before, during, and after spaceflight fail to provide a clear understanding of their characteristics. ex-mtDNA may exist in various forms, such as encapsulated within ex-Mito or completely membrane-free, and the methods of sample collection and handling are critical for accurate analysis. Despite its potential significance, the origins, properties, and health implications of ex-mtDNA and ex-Mito remain largely unexplored in the context of terrestrial and space medicine. This perspective article aims to consolidate existing knowledge, evaluate methodologies for their identification and analysis, and offer critical insights into the biological significance of ex-mtDNA and ex-Mito. By integrating findings from Earth-based studies with the challenges of space exploration, this article seeks to advance our understanding of these novel blood components, laying the groundwork for innovative research in space medicine and strategies to safeguard astronaut health during extended space missions.