TY - JOUR
T1 - Oxygen pathway modeling estimates high reactive oxygen species production above the highest permanent human habitation
AU - Cano, Isaac
AU - Selivanov, Vitaly
AU - Gomez-Cabrero, David
AU - Tegnér, Jesper
AU - Roca, Josep
AU - Wagner, Peter D.
AU - Cascante, Marta
PY - 2014/11/6
Y1 - 2014/11/6
N2 - The production of reactive oxygen species (ROS) from the inner mitochondrial membrane is one of many fundamental processes governing the balance between health and disease. It is well known that ROS are necessary signaling molecules in gene expression, yet when expressed at high levels, ROS may cause oxidative stress and cell damage. Both hypoxia and hyperoxia may alter ROS production by changing mitochondrial Po2 (Pmo2). Because Pmo2 depends on the balance between O2 transport and utilization, we formulated an integrative mathematical model of O2 transport and utilization in skeletal muscle to predict conditions to cause abnormally high ROS generation. Simulations using data from healthy subjects during maximal exercise at sea level reveal little mitochondrial ROS production. However, altitude triggers high mitochondrial ROS production in muscle regions with high metabolic capacity but limited O2 delivery. This altitude roughly coincides with the highest location of permanent human habitation. Above 25,000 ft., more than 90% of exercising muscle is predicted to produce abnormally high levels of ROS, corresponding to the "death zone" in mountaineering.
AB - The production of reactive oxygen species (ROS) from the inner mitochondrial membrane is one of many fundamental processes governing the balance between health and disease. It is well known that ROS are necessary signaling molecules in gene expression, yet when expressed at high levels, ROS may cause oxidative stress and cell damage. Both hypoxia and hyperoxia may alter ROS production by changing mitochondrial Po2 (Pmo2). Because Pmo2 depends on the balance between O2 transport and utilization, we formulated an integrative mathematical model of O2 transport and utilization in skeletal muscle to predict conditions to cause abnormally high ROS generation. Simulations using data from healthy subjects during maximal exercise at sea level reveal little mitochondrial ROS production. However, altitude triggers high mitochondrial ROS production in muscle regions with high metabolic capacity but limited O2 delivery. This altitude roughly coincides with the highest location of permanent human habitation. Above 25,000 ft., more than 90% of exercising muscle is predicted to produce abnormally high levels of ROS, corresponding to the "death zone" in mountaineering.
UR - http://www.scopus.com/inward/record.url?scp=84910623318&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0111068
DO - 10.1371/journal.pone.0111068
M3 - Article
C2 - 25375931
AN - SCOPUS:84910623318
SN - 1932-6203
VL - 9
JO - PLoS One
JF - PLoS One
IS - 11
M1 - 111068
ER -