Chronic obstructive pulmonary disease (
COPD) is a progressive and disabling disorder marked by airflow limitation and extensive destruction of lung parenchyma. Cigarette
smoke is the major risk factor for
COPD development and has been associated with increased
oxidant burden on multiple cell types in the lungs. Elevated levels of
reactive oxygen species (ROS) may significantly affect expression of
biological molecules, signaling pathways, and function of
antioxidant defenses. Although inflammatory cells, such as neutrophils and macrophages, contribute to the release of large quantities of ROS,
mitochondrial dysfunction plays a critical role in ROS production due to oxidative phosphorylation. Although mitochondria are dynamic organelles, excess oxidative stress is able to alter mitochondrial function, morphology, and
RNA and
protein content. Indeed, mitochondria may change their shape by undergoing fusion (regulated by mitofusin 1, mitofusin 2, and
optic atrophy 1 proteins) and fission (regulated by
dynamin-related
protein 1), which are essential processes to maintain a healthy and functional mitochondrial network. Cigarette
smoke can induce mitochondrial hyperfusion, thus reducing mitochondrial quality control and cellular stress resistance. Furthermore, diminished levels of
enzymes involved in the mitophagy process, such as Parkin (a
ubiquitin ligase E3) and the
PTEN-induced putative kinase 1 (PINK1), are commonly observed in
COPD and correlate directly with faulty removal of dysfunctional mitochondria and consequent cell senescence in this disorder. In this review, we highlight the main mechanisms for the regulation of mitochondrial quality and how they are affected by oxidative stress during
COPD development and progression.