Metabolism and bioenergetics in the pathophysiology of organ fibrosis

Fibrosis is the tissue scarring characterized by excess deposition of extracellular matrix (ECM) proteins, mainly collagens. A fibrotic response can take place in any tissue of the body and is the result of an imbalanced reaction to inflammation and wound healing. Metabolism has emerged as a major driver of fibrotic diseases. While glycolytic shifts appear to be a key metabolic switch in activated stromal ECM-producing cells, several other cell types such as immune cells, whose functions are intricately connected to their metabolic characteristics, form a complex network of pro-fibrotic cellular crosstalk. This review purports to clarify shared and particular cellular responses and mechanisms across organs and etiologies. We discuss the impact of the cell-type specific metabolic reprogramming in fibrotic diseases in both experimental and human pathology settings, providing a rationale for new therapeutic interventions based on metabolism-targeted antifibrotic agents.