Mitochondrial bioenergetics and pulmonary dysfunction: Current progress and future directions.

This review summarizes current understanding of mitochondrial bioenergetic dysfunction applicable to mechanisms of lung diseases and outlines challenges and future directions in this rapidly emerging field. Although the role of mitochondria extends beyond the term of cellular "powerhouse", energy generation remains the most fundamental function of these organelles. It is not counterintuitive to propose that intact energy supply is important for favorable cellular fate following pulmonary insult. In this review, the discussion of mitochondrial dysfunction focuses on those molecular mechanisms that alter cellular bioenergetics in the lungs: (a) inhibition of mitochondrial respiratory chain, (b) mitochondrial leak and uncoupling, (c) alteration of mitochondrial Ca handling, (d) mitochondrial production of reactive oxygen species and self-oxidation. The discussed lung diseases were selected according to their pathological nature and relevance to pediatrics: Acute lung injury (ALI), defined as acute parenchymal lung disease associated with cellular demise and inflammation (Acute Respiratory Distress Syndrome, ARDS, Pneumonia), alveolar developmental failure (Bronchopulmonary Dysplasia, BPD or chronic lung disease in premature infants), obstructive airway diseases (Bronchial asthma) and vascular remodeling affecting pulmonary circulation (Pulmonary Hypertension, PH). The analysis highlights primary mechanisms of mitochondrial bioenergetic dysfunction contributing to the disease-specific pulmonary insufficiency and proposes potential therapeutic targets.