Pleiotropic roles of evolutionarily conserved signaling intermediate in toll pathway (ECSIT) in pathophysiology

Abstract

The evolutionarily conserved signaling intermediate in toll pathway (ECSIT) is a cytosolic adaptor protein associated with the toll‐like receptor pathway. It has a distinct N‐terminal mitochondrial targeting sequence, pentatricopeptide repeat motif, and a C‐terminal pleckstrin homology domain. ECSIT regulates many biological processes like embryonic development, inflammation, cardiac function, and assembly of mitochondrial complex I. Besides, ECSIT also interacts with multiple signaling intermediates like tumor necrosis receptor associated factor 6 and retinoic acid inducible gene 1 as well as regulates various pathways in the microcellular environment. However, molecular details of ECSIT functions in pathophysiology remain elusive. This review summarizes the diverse functions of ECSIT and its involvement in pathophysiological conditions such as Alzheimer's, oxidative stress, and infection.

Mitochondria in innate immunity signaling and its therapeutic implications in autoimmune diseases

“…Other biochemical reactions, such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) complexes and uncoupled nitric oxide synthase reactions at the meantime also generate certain amounts of non-m ROS, especially in phagocytic cells, including macrophages, DCs, and neutrophils ( 18 – 20 ). Studies have shown that the activation of TLRs in innate immune cells sends signals via tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and evolutionarily conserved signaling intermediate in toll pathways (ECSIT), leading to the phagocytosis of mitochondria and eventually contributing to mROS production ( 21 ). The NLR family, another class of cytoplasmic PRRs, also potentially increases mROS levels upon its activation through downstream regulators, such as NLRP3 inflammasomes and NLRX1 ( 22 ).…”