The Roles of Mitochondrial Damage-Associated Molecular Patterns in Diseases

TLDR

Mitochondria generate cellular energy and release damage‑associated molecular patterns (DAMPs) such as proteins, DNA, and lipids during cell death, which trigger inflammatory responses and are linked to the severity and prognosis of diseases including infection, asthma, ischemic heart disease, and cancer. The study aims to clarify how mitochondrial DAMPs are released into extracellular spaces and exert biological functions in vivo, and to investigate whether targeting these pathways could yield new therapeutics. Researchers examine the secretion of multiple DAMP types during cell death, their synergistic interactions, and the regulation of mitochondrial DAMP‑mediated immune responses that may influence disease progression. Measuring mitochondrial DAMPs in patients shows promise as biomarkers for predicting prognosis or therapeutic response. Antioxid.

Abstract

Mitochondria, vital cellular power plants to generate energy, are involved in immune responses. Mitochondrial damage-associated molecular patterns (DAMPs) are molecules that are released from mitochondria to extracellular space during cell death and include not only proteins but also DNA or lipids. Mitochondrial DAMPs induce inflammatory responses and are critically involved in the pathogenesis of various diseases.Recent studies elucidate the molecular mechanisms by which mitochondrial DAMPs are released and initiate immune responses by use of genetically modulated cells or animals. Importantly, the levels of mitochondrial DAMPs in patients are often associated with severity and prognosis of human diseases, such as infection, asthma, ischemic heart disease, and cancer.Although mitochondrial DAMPs can represent proinflammatory molecules in various experimental models, their roles in human diseases may be multifunctional and complex. It remains unclear where and how mitochondrial DAMPs are liberated into extracellular spaces and exert their biological functions particularly in vivo. In addition, while mitochondria can secrete several types of DAMPs during cell death, the interaction of each mitochondrial DAMP (e.g., synergistic effects) remains unclear.Regulation of mitochondrial DAMP-mediated immune responses may be important to alter the progression of human diseases. In addition, measuring mitochondrial DAMPs in patients may be clinically useful as biomarkers to predict prognosis or response to therapies. Further studies of the mechanisms by which mitochondrial DAMPs impact the initiation and progression of diseases may lead to the development of therapeutics specifically targeting this pathway. Antioxid.