TY - UNPB
T1 - Guardians of the Mitochondria
T2 - Space Mitochondria 2.0 Systemic Analysis Reveals Bioenergetic Dysregulation Across Species
AU - Guarnieri, Joseph
AU - Maghsoudi, Zeynab
AU - Kim, Jangkeun
AU - Bya, Phi
AU - Widjaja, Gabrielle
AU - Barker, Richard
AU - Burke, Marissa
AU - Cen, Zimu
AU - Fazelinia, Hossein
AU - Tsoy, Sergey
AU - Tiersky, Rachel
AU - Peczak, Anna
AU - Kim, Jihan
AU - Kim, Ye-Ah
AU - Haltom, Jeffrey
AU - Almeida, Michael
AU - Garris, Michael A.
AU - Day, Sarah
AU - Sanchez-Hodge, Rebekah
AU - Zilberman, Aleeza H.
AU - Allen, Noah G.
AU - Kukib, Angela J.
AU - Blaber, Elizabeth A.
AU - Mathyk, Begum
AU - Harris, Frederick C.
AU - Singh, Kanhaiya
AU - Sen, Chandan K.
AU - Innes, Lucinda
AU - Ali, Nilufar
AU - Berliner, Aaron J.
AU - Kar, Upendra
AU - Overbey, Eliah
AU - Giunta, Simona
AU - Podrabsky, Jason E.
AU - Neal, Matthew D.
AU - Billiar, Timothy R.
AU - Headley, Colwyn
AU - Meydan, Cem
AU - Tasoula, Alexia
AU - Szewczyk, Nathaniel J.
AU - Ikeda, Yasutaka
AU - Gotoh-Katoh, Aina
AU - Schisler, Jonathan C.
AU - Kim, Man S.
AU - Schwartz, Robert E.
AU - Wallace, Douglas C.
AU - Mason, Christopher E.
AU - Nguyen, Tin
AU - Beheshti, Afshin
N1 - This is a preprint article. It offers immediate access but has not been peer reviewed.
PY - 2025/1
Y1 - 2025/1
N2 - Spaceflight imposes unique stressors that disrupt mitochondrial function, vital for energy production and immune regulation. Our multi-omics analysis (proteomics, bisulfite sequencing, RNA-seq, and single-nuclei RNA/ATAC-seq) on astronauts, rodents, and model organisms (flies, worms, plants) revealed progressive impairment of mitochondrial oxidative phosphorylation (OXPHOS) during spaceflight, with delayed recovery post-return across species. In rodents, radiation ≥10.34 mGy activated persistent mitochondrial stress pathways across multiple organs except in the spleen, with older and male C57BL/6 mice most affected. Astronaut data from the NASA Twins Study, JAXA, and Inspiration4 missions showed prolonged mitochondrial dysfunction, with OXPHOS suppression and TCA cycle inhibition lasting up to 82 days. Bisulfite sequencing confirmed lasting epigenetic changes in OXPHOS genes. Lastly, Kaempferol, an antioxidant and mitochondrial activator, mitigated radiation-induced liver atrophy in mice and preserved liver function in human organoids. This cross-species study underscores the need for targeted therapies to protect mitochondrial biogenesis during long-duration space missions.
AB - Spaceflight imposes unique stressors that disrupt mitochondrial function, vital for energy production and immune regulation. Our multi-omics analysis (proteomics, bisulfite sequencing, RNA-seq, and single-nuclei RNA/ATAC-seq) on astronauts, rodents, and model organisms (flies, worms, plants) revealed progressive impairment of mitochondrial oxidative phosphorylation (OXPHOS) during spaceflight, with delayed recovery post-return across species. In rodents, radiation ≥10.34 mGy activated persistent mitochondrial stress pathways across multiple organs except in the spleen, with older and male C57BL/6 mice most affected. Astronaut data from the NASA Twins Study, JAXA, and Inspiration4 missions showed prolonged mitochondrial dysfunction, with OXPHOS suppression and TCA cycle inhibition lasting up to 82 days. Bisulfite sequencing confirmed lasting epigenetic changes in OXPHOS genes. Lastly, Kaempferol, an antioxidant and mitochondrial activator, mitigated radiation-induced liver atrophy in mice and preserved liver function in human organoids. This cross-species study underscores the need for targeted therapies to protect mitochondrial biogenesis during long-duration space missions.
U2 - 10.2139/ssrn.5087025
DO - 10.2139/ssrn.5087025
M3 - Preprint
BT - Guardians of the Mitochondria
ER -