Molecular and Genetic Medicine

A Possible Link between Dysregulated Mitochondrial Calcium Homeostasis and Citrullination in Rheumatoid Arthritis

Abstract

Gautam S, Goswami A, Chaurasia P and Dada R

Rheumatoid arthritis (RA) is characterized by citrullination of peptides and proteins mediated by calciumdependent peptidyl arginine deiminase enzymes (PADs). Various mechanisms of intracellular and extracellular protein citrullination have been elucidated so far. Here, we highlight one more important possible mechanism that could lead to intracellular citrullination due to dysregulated mitochondrial Ca2+ homeostasis i.e., inability of mitochondrial uptake of Ca2+ during physiological signaling and triggering the generation of autoimmune disease. Spontaneous secretion of intracellular PAD may be the result of high cytosolic Ca2+ due to a disturbance in mitochondrial calcium homeostasis secondary to oxidative damage without any compromise to the cell membrane. Various environmental triggers like air pollutants also induce oxidative stress (OS) which may compromise the mitochondrial integrity and disturb Ca2+ homeostasis. Adoption of simple lifestyle modification like yoga and meditation optimizes reactive oxygen species (ROS) levels and maintains mitochondrial integrity by increasing COX activity, thus may curb citrullination process and its sequelae.