The mitochondrion is the main site of energy production and a
hub of key signaling pathways. It is also central in stress-adaptive
response due to its dynamic morphology and ability to interact
with other organelles. In response to stress, mitochondria fuse
into networks to increase bioenergetic efficiency and protect
against oxidative damage. Mitochondrial damage triggers
segregation of damaged mitochondria from the mitochondrial
network through fission and their proteolytic degradation by
mitophagy. Post-translational modifications of the
mitochondrial proteome and nuclear cross-talk lead to
reprogramming of metabolic gene expression to maintain energy
production and redox balance. Chronic obstructive pulmonary
disease (COPD) is caused by chronic exposure to oxidative
stress arising from inhaled irritants, such as cigarette smoke.
Impaired mitochondrial structure and function, due to
oxidative stress–induced damage, may play a key role in
causing COPD. Deregulated metabolic adaptation may
contribute to the development and persistence of mitochondrial
dysfunction in COPD. We discuss the evidence for deregulated
metabolic adaptation and highlight important areas for
investigation that will allow the identification of molecular
targets for protecting the COPD lung from the effects of
dysfunctional mitochondria.