Mitochondrial Dysfunction in Chronic Respiratory Diseases: Implications for the Pathogenesis and Potential Therapeutics

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.

Regulatory roles of external cholesterol in human airway epithelial mitochondrial function through STARD3 signalling

“… 14 Oxidative stress, mitophagy and mitochondrial dynamics including fusion and fission were found to play crucial roles in COPD and serve as therapeutic targets. 15 , 16 Of various metabolic pathways, mitochondria play a key role in lipid metabolism, cholesterol homeostasis and interactions among intracellular organelles, 17 , 18 , 19 although the exact mechanism in COPD remains unclear. The aim of the present study was to investigate alterations of cholesterol metabolism in COPD and potential mechanisms by which cholesterol regulated mitochondrial function in lung epithelial cells.…”

“…14 Oxidative stress, mitophagy and mitochondrial dynamics including fusion and fission were found to play crucial roles in COPD and serve as therapeutic targets. 15,16 Of various metabolic pathways, F I G U R E 1 Cholesterol overload and inflammation in cells and animals with smoking and in patients with chronic obstructive pulmonary diseases (COPDs). The cholesterol level was detected by Gas Chromatography-Mass Spectrometry (GC-MS)/MS metabolomics in the plasma of COPD patients (n = 22) and healthy volunteers (n = 19) (A).…”

“…Increasing evidence suggests an important role of mitochondrial dysfunction in the pathogenesis and development of lung diseases 14 . Oxidative stress, mitophagy and mitochondrial dynamics including fusion and fission were found to play crucial roles in COPD and serve as therapeutic targets 15,16 . Of various metabolic pathways, mitochondria play a key role in lipid metabolism, cholesterol homeostasis and interactions among intracellular organelles, 17–19 although the exact mechanism in COPD remains unclear.…”

Мітохондріальна Дисфункція У Загальному Континуумі Неінфекційних Захворювань Із Позиції Системної Медицини. Частина I. Огляд Літератури І Результати Теоретичного Дослідження

“…Таким чином, мітохондрії задіяні у значній кількості епігенетичних процесів людського тіла, мають ключове енергетично-метаболічне значення для існування клітини і забезпечення можливості реалізації феномену життя. Також існує значна кількість наукових досліджень стосовно патогенетичної ролі розладів функцій мітохон дрій майже при всіх набутих захворюваннях внутрішніх органів шлунково-кишкової [12,45,56,60], дихальної [44,53,61], сечо статевої [59], серцево-судинної [38,[62][63][64][65][66][67] систем, онкологічних процесах [46,56,[68][69][70], ендокринних розладах [38,58,71,72], нейродегенеративних захворюваннях [29-31, 33, 36, 37, 40, 73], в педіатрії [60,[74][75][76] тощо. Це вказує на системність і на шлях виникнен ня коморбідності при НІЗ за рахунок мітохондріальної пато логії.…”

Cellular Senescence in Aging Lungs and Diseases

“…Mitochondrial oxidative stress has been thought to be involved in accelerating aging effects. Separately, mitochondrial oxidative stress has been associated with lung diseases such as COPD and IPF and could thus play a role in stimulating as well as maintaining cellular senescence towards impaired lung function [ 8 , 9 , 10 ].…”