Idiopathic pulmonary fibrosis (IPF) and other forms of lung fibrosis are age-associated
diseases with increased deposition of mesenchymal collagen that promotes respiratory
malfunction and eventual death from respiratory failure. Our understanding of the
pathobiology underlying pulmonary fibrosis is incomplete and current therapies available
to slow or treat lung fibrosis are limited. Evidence reviewed herein demonstrates
key involvement of mitochondrial dysfunction in diverse pulmonary cell populations,
including alveolar epithelial cells (AEC), fibroblasts, and macrophages and/or immune
cells that collectively advances the development of pulmonary fibrosis. The mitochondria
have an important role in regulating whether fibrogenic stimuli results in the return
of normal healthy function ("friend") or the development of pulmonary fibrosis ("foe").
In particular, we summarize the evidence suggesting that AEC mitochondrial dysfunction
is important in mediating lung fibrosis signaling via mechanisms involving imbalances
in the levels of reactive oxygen species, endoplasmic reticulum stress response, mitophagy,
apoptosis and/or senescence, and inflammatory signaling. Further, we review the emerging
evidence suggesting that dysfunctional mitochondria in AECs and other cell types play
crucial roles in modulating nearly all aspects of the 9 hallmarks of aging in the
context of pulmonary fibrosis as well as some novel molecular pathways that have recently
been identified. Finally, we discuss the potential translational aspects of these
studies as well as the key knowledge gaps necessary for better informing our understanding
of the pathobiology of the mitochondria in mediating pulmonary fibrosis. We reason
that targeting deficient mitochondria-derived pathways may provide innovative future
treatment strategies that are urgently needed for lung fibrosis.
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Article info
Publication history
Published online: June 23, 2018
Accepted:
May 27,
2018
Received in revised form:
May 24,
2018
Received:
April 13,
2018
Identification
Copyright
© 2018 Elsevier Inc. All rights reserved.
