Mitochondrial Function in Lung Health and Disease

The mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. In addition to supplying cellular energy, mitochondria are involved in a range of other processes, such as signaling and cell death. The mitochondrion is able to sense PO2 throughout the progressive reduction of cytochrome c with increasing hypoxia. This information is converted into an increase in reactive oxygen species production at complex III that acts as cell signal. Such signal is believed to be responsible for phenomena such as hypoxic vasoconstriction, activation of HIF, and internalization of the sodium-potassium pump of the alveolar epithelium. Mitochondrial DNA mutations are frequent in cancer cells. These mutations lead to an impaired oxidative metabolism and to decreased susceptibility to apoptosis. These two features are needed for survival of the cancer cell. There are two major signaling pathways of apoptosis and one of them involves the mitochondria. Apoptosis plays an important role in most lung diseases in two different ways. First, failure to clear unwanted cells by apoptosis will prolong the inflammation; second, excessive apoptosis may cause diseases. Finally the skeletal muscle dysfunction associated with COPD involves the loss of oxidative capacity, mainly due to the loss of mitochondrial density.