Role of mitochondrial dysfunction on rheumatic diseases

Abstract

Rheumatic and musculoskeletal diseases are a heterogeneous group of disorders affecting joint tissues and in some cases even organs, some of them being among the most common diseases worldwide. Mitochondria are the organelles considered as powerhouse of cells providing energy to the organism mainly through oxidative phosphorylation. However, mitochondria are also involved in crucial pathways responsible for maintaining cell physiology, such as the activation of metabolic and survival signaling, and innate and adaptive immune response. As consequence of the pivotal role of mitochondria in cell homeostasis, an impairment of mitochondrial function has been associated with activation of pathological events, including oxidative stress and subsequently damaged protein and DNA, deregulation of programmed cell death, and over-activation of inflammatory responses modulated by redox-sensitive signaling or direct activation of the inflammasome. Thus, a growing amount of evidence emphasizes the role of mitochondria in aging and inflammatory-related diseases, including rheumatic disorders. In this regard, emerging findings suggest that targeting of the pathways involved in the maintenance of mitochondrial metabolism may control cell homeostasis, and in turn delay ageing and prevent or improve articular pathologies. In this review we will focus on the importance of mitochondria in metabolic homeostasis of articular cells, as well as their influence on the activation of pathological signaling pathways, as a result of a genetic predisposition, damage, decline or impairment of their function. Finally, we will discuss some of the most important evidences of involvement of mitochondria in the onset and progression of rheumatic diseases.

Keywords: Cell death; Immunometabolism; Inflammasome; Mitochondria; Oxidative stress; Rheumatic diseases.