Abstract
Mitochondria are indispensable for energy metabolism and cell signaling. Mitochondrial homeostasis is sustained with stabilization of mitochondrial membrane potential, balance of mitochondrial calcium, integrity of mitochondrial DNA, and timely clearance of damaged mitochondria via mitophagy. Mitochondrial dysfunction is featured by increased generation of mitochondrial reactive oxygen species, reduced mitochondrial membrane potential, mitochondrial calcium imbalance, mitochondrial DNA damage, and abnormal mitophagy. Accumulating evidence indicates that mitochondrial dysregulation causes oxidative stress, inflammasome activation, apoptosis, senescence, and metabolic reprogramming. All these cellular processes participate in the pathogenesis and progression of chronic respiratory diseases, including chronic obstructive pulmonary disease, pulmonary fibrosis, and asthma. In this review, we provide a comprehensive and updated overview of the impact of mitochondrial dysfunction on cellular processes involved in the development of these respiratory diseases. This not only implicates mechanisms of mitochondrial dysfunction for the pathogenesis of chronic lung diseases but also provides potential therapeutic approaches for these diseases by targeting dysfunctional mitochondria.
Highlights
Mitochondria are subcellular organelles that originate from a bacterial symbiont, containing two separate and functionally distinct outer and inner membranes that separate the intermembrane space and matrix compartment [1, 2]
Mitochondria differ from other organelles and have their own maternally inherited DNA [4]. mtDNA contains 37 genes coded for two ribosomal RNAs, 22 transfer RNAs, and the remainder 13 encoding proteins involved in oxidative phosphorylation (OXPHOS)
Mitochondrial calcium in MCUsilenced cells is significantly reduced to levels similar to that in unexposed cells. These findings suggest that the increased activity of mitochondrial calcium uniporter (MCU) along with the overload of mitochondrial calcium in lung macrophages promotes the pathogenesis of pulmonary fibrosis [170]
Summary
Mitochondria are subcellular organelles that originate from a bacterial symbiont, containing two separate and functionally distinct outer and inner membranes that separate the intermembrane space and matrix compartment [1, 2] It is considered the powerhouse of cells with energy generation in the forms of adenosine 5′-triphosphate (ATP) via oxidative phosphorylation (OXPHOS) on the electron transport chain (ETC) [3]. Once mitochondrial homeostasis is disrupted, it can disturb the OXPHOS process and induce accumulation and generation of side products, including ROS, which further cause mitochondrial dysfunction, forming a vicious cycle harmful to cell function [14]. Mitochondrial homeostasis can be disrupted by environmental insults including tobacco smoke, air pollutants, inflammation, infection, hypoxia, and hyperoxia, resulting in mitochondrial dysfunction This is characterized by increased mtROS, reduced MMP, mtDNA damage and release, and abnormal calcium signaling and storage. This enhances understanding of mechanisms of mitochondrial dysfunction underlying the pathogenesis of chronic respiratory diseases and suggests potential therapeutic approaches for these diseases by targeting dysregulated mitochondria
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
