Prof Bruno Grassi
Department of Medicine
University of Udine
Udine, Italy

Oxidative metabolism and mitochondrial function in simulated and actual spaceflight

Bruno Grassi¹, Giovanni Baldassarre¹, Uroš Marúsič², Bostjan Siminič², Gianni Biolo³, Marco Narici⁴, Rado Pišot², Lucrezia Zuccarelli¹

¹Department of Medicine, University of Udine, Udine, Italy,
²Science and Research Centre Koper, Slovenia,
³Department of Medical Sciences, University of Trieste, Italy,
⁴Department of Biomedical Sciences, University of Padua, Italy

Skeletal muscle oxidative metabolism and mitochondrial function represent “the last step” in the long pathway for O2, from ambient air to oxidative phosphorylation. This metabolism is often neglected in studies dealing with the effects of microgravity/disuse on skeletal muscle, which mainly take into consideration muscle mass and muscle force. This is unfortunate, considering that all activities lasting longer than 1-2 minutes substantially rely on oxidative metabolism for ATP turnover. Apart from its direct effects on exercise tolerance, a decreased “cardiorespiratory fitness” determined by microgravity/disuse, as identified by the a decreased maximal O2 uptake (V̇O2max), is associated with profound negative consequences on the general health status of the subjects, such as decreased insulin sensitivity, “pro-inflammatory” condition, impaired endothelial function, mitochondrial dysfunction, altered function of the neuromuscular junction, altered redox status, increased oxidative stress. A V̇O2max decrease during microgravity/disuse has been described in “bed rest” studies, ranging from hours to a few months. These studies have allowed to identify “bottlenecks” along the O2 transport and O2 utilization pathway, mainly related to impaired cardiac function, reduced blood volume, impaired microvascular/endothelial function. These impairments would occur relatively early during exposure, whereas peripheral O2 conductance and mitochondrial respiration would be significantly affected during longer exposures. There are, however, areas in which bed rest studies appear to be relatively weak in terms of the inferences on real spaceflight conditions, in relation to the significantly longer durations of space missions, to the role of in-flight countermeasures (e.g. exercise, artificial gravity), to the very relevant role played by space radiations.

According to recent work from our group short periods if microgravity/disuse could have an interesting effect on skeletal muscle and whole body oxidative metabolism in resting conditions, that is a substantial decrease in resting muscle V̇O2 and whole-body resting energy expenditure (REE). Even by being far less pronounced compared to the typical reduction of REE observed in obligate hibernating animals, the observed inactivity-related decrease in resting muscle V̇O2 and REE, possibly aimed at preventing ATP accumulation or excessive ROS production, could mitigate numerous biological and logistic challenges of prolonged spaceflights by lowering rates of crewmember consumable use (food, water, O2) and CO2 production. On the other hand, the inactivity-related decrease in REE would have negative consequences on the health status of subjects, by altering body mass homeostasis and increasing the risk of metabolic diseases.