The Role of Interaction between Mitochondria and the Extracellular Matrix in the Development of Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a condition which affects mainly older adults, that suggests mitochondrial dysfunction and oxidative stress, which follow cells senescence, and might contribute to the disease onset. We have assumed pathogenesis associated with crosstalk between the extracellular matrix (ECM) and mitochondria, mainly based on mitochondrial equilibrium impairment consisting of (1) tyrosine kinases and serine-threonine kinase (TKs and ST-Ks) activation via cytokines, (2) mitochondrial electron transport chain dysfunction and in consequence electrons leak with lower ATP synthesis, (3) the activation of latent TGF-β via αVβ6 integrin, (4) tensions transduction via α2β1 integrin, (5) inefficient mitophagy, and (6) stress inhibited biogenesis. Mitochondria dysfunction influences ECM composition and vice versa. Damaged mitochondria release mitochondrial reactive oxygen species (mtROS) and the mitochondrial DNA (mtDNA) to the microenvironment. Therefore, airway epithelial cells (AECs) undergo transition and secrete cytokines. Described factors initiate an inflammatory process with immunological enhancement. In consequence, local fibroblasts exposed to harmful conditions transform into myofibroblasts, produce ECM, and induce progression of fibrosis. In our review, we summarize numerous aspects of mitochondrial pathobiology, which seem to be involved in the pathogenesis of lung fibrosis. In addition, an increasing body of evidence suggests considering crosstalk between the ECM and mitochondria in this context. Moreover, mitochondria and ECM seem to be important players in the antifibrotic treatment of IPF.

Machine learning-based prediction of candidate gene biomarkers correlated with immune infiltration in patients with idiopathic pulmonary fibrosis

“…Although numerous related studies have been reported, the mechanisms underlying the onset and development of IPF remain unclear (37). Epithelialmesenchymal transition, ECM deposition and lung remodelling may be involved in the onset and progression of IPF (38)(39)(40).…”

Silencing TUFM Inhibits Development of Monocrotaline-Induced Pulmonary Hypertension by Regulating Mitochondrial Autophagy via AMPK/mTOR Signal Pathway

“…The pathological mainly includes the excessive proliferation and/or apoptosis resistance of PASMCs as well as the accumulation of extracellular matrix components such as collagen and elastin. Mitochondria as the central guardian of mitochondrial homeostasis orchestrate diverse cellular processes including cell cycle progression, mitochondrial dynamics, the cell metabolism, and even the extracellular matrix components [ 27 , 28 ], which closely connected the pathogenesis and pathology of PAH. TUFM serves as an important factor in the translational expression of mitochondrial DNA and plays a key role in the control of mitochondrial function.…”

Automated analysis of mitochondrial dimensions in mesenchymal stem cells: Current methods and future perspectives

“…A deficiency in the synthesis of the mitochondrial-encoded subunits of the respiratory chain alters the ECM composition in cartilage tissue, resulting in collagen crosslinking and an increased ECM stiffness [ 12 ]. The ability of mitochondria to adapt to mechanical stressors in the microenvironment has also been associated with several pathologies, reviewed elsewhere [ [13] , [14] , [15] ]. Organ-on-a-chip or tissue-on-a-chip in combination with microfluidics maintain the integrity of the sample preserving organelle function.…”