Mitochondrial dynamics and mitophagy in lung disorders

Abstract

Mitochondria are biosynthetic, bioenergetic, and signaling organelles which are critical for physiological adaptations and cellular stress responses to the environment. Various endogenous and environmental stress affects critical processes in mitochondrial homeostasis such as oxidative phosphorylation, biogenesis, mitochondrial redox system which leads to the formation of reactive oxygen species (ROS) and free radicals. The state of function of the mitochondrion is particularly dependent on the dynamic balance between mitochondrial biogenesis, fusion and fission, and degradation of damaged mitochondria by mitophagy. Increasing evidence has suggested a prominent role of mitochondrial dysfunction in the onset and progression of various lung pathologies, ranging from acute to chronic disorders. In this comprehensive review, we discuss the emerging findings of multifaceted regulations of mitochondrial dynamics and mitophagy in normal lung homeostasis as well as the prominence of mitochondrial dysfunction as a determining factor in different lung disorders such as lung cancer, COPD, IPF, ALI/ARDS, BPD, and asthma. The review will contribute to the existing understanding of critical molecular machinery regulating mitochondrial dynamic state during these pathological states. Furthermore, we have also highlighted various molecular checkpoints involved in mitochondrial dynamics, which may serve as hopeful therapeutic targets for the development of potential therapies for these lung disorders.

Keywords: Lung disorders; Mitochondrial dynamics; Mitochondrial fission; Mitochondrial fusion; Mitophagy.