Early heart and skeletal muscle mitochondrial response to a moderate hypobaric hypoxia environment Aragón Vela, Jerónimo Casuso, Rafael A. Sagrera Aparisi, Ana Plaza Díaz, Julio Ramón Rueda-Robles, Ascensión Hidalgo Gutiérrez, Agustín López García, Luis Carlos Rodriguez-Carrillo, Andrea Enriquez, José Antonio Cogliati, Sara Rodríguez Huertas, Jesús Francisco heart mitochondria moderate hypobaric hypoxia In eukaryotic cells, aerobic energy is produced by mitochondria through oxygen uptake. However, little is known about the early mitochondrial responses to moderate hypobaric hypoxia (MHH) in highlymetabolic active tissues. Here, we describe the mitochondrial responses to acute MHH in the heart and skeletalmuscle. Rats were randomly allocated into a normoxia control group (n = 10) and a hypoxia group (n = 30), divided into three groups (0, 6, and 24 h post-MHH). The normoxia situation was recapitulated at the University of Granada, at 662 m above sea level. The MHH situation was performed at the High-Performance Altitude Training Centre of Sierra Nevada located inGranada at 2320mabove sea level.We found a significant increase inmitochondrial supercomplex assembly in the heart as soon as the animals reached 2320mabove sea level and their levels are maintained 24 h post-exposure, but not in skeletal muscle. Furthermore, in skeletal muscle, at 0 and 6 h, therewas increased dynamin-related protein 1 (Drp1) expression and a significant reduction inMitofusin 2. In conclusion,mitochondria from themuscle and heart respond differently toMHH: mitochondrial supercomplexes increase in the heart, whereas, in skeletal muscle, the mitochondrial pro-fission response is trigged. Considering that skeletal muscle was not actively involved in the ascent when the heart was beating faster to compensate for the hypobaric, hypoxic conditions, we speculate that the different responses toMHH are a result of the different energetic requirements of the tissues upon MHH. 2025-01-08T11:58:40Z 2025-01-08T11:58:40Z 2024-04-17 journal article Aragón Vidal, J. et. al. J Physiol 602.21 (2024) pp 5631–5641. [https://doi.org/10.1113/JP285516] https://hdl.handle.net/10481/98698 10.1113/JP285516 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Wiley Online Library