Mitochondrial proteomics reveals reductive metabolism dependent on glutamine in fibroblasts of idiopathic pulmonary fibrosis under hypoxia

ABSTRACT: Pulmonary fibrosis, particularly idiopathic pulmonary fibrosis (IPF), is a chronic disease characterized not only by a transcriptionally active signature associated with hypoxia but also by feedback loops that may underlie disease progression. IPF fibroblasts are known to contribute to disease by the pronounced differentiation of fibroblasts into myofibroblasts results in the accumulation of extracellular matrix, creating a hypoxic microenvironment that supports the characteristic phenotype observed in the fibroblasts of these patients. Although several changes have been linked to fibroblast metabolism, the hypoxic conditions that are present in mitochondria generally go unreported. This study aimed to characterize the differences in the mitochondrial proteomic profile between healthy lung fibroblasts and those affected by IPF under hypoxic conditions. Methods. Mitochondria were isolated and evaluated by electron microscopy and western blotting, and the proteomic profile using the label-free proteomics. Results. Our results revealed that in controls, there is a metabolism of fatty acids and acetyl-CoA regulation, with a slight increase in mitophagy to utilize different substrates as energy sources in an appropriate response to low oxygen conditions. In contrast, the mitochondria of fibroblasts from patients with IPF show a particular adaptation in glutamine metabolism, which may participate in their commitment to myofibroblast differentiation. Conclusions. These findings underscore the importance of these proteins in the mitochondrial context, providing a foundation for further investigations into their functions and potential involvement in specific biological processes.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Fibroblast

DISEASE(S): Idiopathic Pulmonary Fibrosis

SUBMITTER: Emmanuel Rios-Castro  

LAB HEAD: Arnoldo Aquino Gálvez

PROVIDER: PXD064472 | Pride | 2025-11-05

REPOSITORIES: Pride