Abstract
Iron deficiency (ID), with or without anemia, is responsible for physical fatigue. This effect may be linked to an alteration of mitochondrial metabolism. Our aim was to assess the impact of ID on skeletal striated muscle mitochondrial metabolism. Iron-deficient non-anemic mice, obtained using a bloodletting followed by a low-iron diet for three weeks, were compared to control mice. Endurance was assessed using a one-hour submaximal exercise on a Rotarod device and activities of mitochondrial complexes I and IV were measured by spectrophotometry on two types of skeletal striated muscles, the soleus and the quadriceps. As expected, ID mice displayed hematologic markers of ID and reduced iron stores, although none of them were anemic. In ID mice, endurance was significantly reduced and activity of the respiratory chain complex I, normalized to citrate synthase activity, was significantly reduced in the soleus muscle but not in the quadriceps. Complex IV activities were not significantly different, neither in the soleus nor in the quadriceps. We conclude that ID without anemia is responsible for impaired mitochondrial complex I activity in skeletal muscles with predominant oxidative metabolism. These results bring pathophysiological support to explain the improved physical activity observed when correcting ID in human. Further studies are needed to explore the mechanisms underlying this decrease in complex I activity and to assess the role of iron therapy on muscle mitochondrial metabolism.