Mitochondrial network dynamics in pulmonary disease: Bridging the gap between inflammation, oxidative stress, and bioenergetics.

ABSTRACT

Once thought of in terms of bioenergetics, mitochondria are now widely accepted as both the orchestrator of cellular health and the gatekeeper of cell death. The pulmonary disease field has performed extensive efforts to explore the role of mitochondria in regulating inflammation, cellular metabolism, apoptosis, and oxidative stress. However, a critical component of these processes needs to be more studied mitochondrial network dynamics. Mitochondria morphologically change in response to their environment to regulate these processes through fusion, fission, and mitophagy. This allows mitochondria to adapt their function to respond to cellular requirements, a critical component in maintaining cellular homeostasis. For that reason, mitochondrial network dynamics can be considered a bridge that brings multiple cellular processes together, revealing a potential pathway for therapeutic intervention. In this review, we discuss the critical modulators of mitochondrial dynamics and how they are affected in pulmonary diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), acute lung injury (ALI), and pulmonary arterial hypertension (PAH). A dysregulated mitochondrial network plays a crucial role in lung disease pathobiology, and aberrant fission/fusion/mitophagy pathways are druggable processes that warrant further exploration. Thus, we also discuss the candidates for lung disease therapeutics that regulate mitochondrial network dynamics.