The Role of Mitochondria-Associated Endoplasmic Reticulum Membranes in Fibrotic Diseases

Abstract

Fibrotic diseases are characterized by high incidence and mortality rates, posing substantial challenges to global public health due to their considerable disease burden. Mitochondrial damage is a common feature in all fibrotic diseases. Mitochondria do not function in isolation; rather, they are often influenced by stress signals from adjacent organelles. Mitochondria and the endoplasmic reticulum are frequently studied as a subfunctional unit. Mitochondria-associated endoplasmic reticulum membranes (MAM) serve as physical connectors between mitochondria and the endoplasmic reticulum. MAM plays a pivotal role in multiple pathological and physiological processes, including lipid metabolism, inflammation, mitochondrial function, cell death, and cellular senescence. These pathological processes are also implicated in the progression of fibrotic diseases. In this review, we examine the relationship between MAM and key pathological mechanisms in fibrotic diseases, such as cell death, cellular senescence, and inflammation. We further explore the potential of MAM as diagnostic biomarkers and therapeutic targets for fibrotic diseases, thereby offering novel research directions and treatment strategies aimed at improving outcomes for patients with fibrotic diseases.