STING1 in Different Organelles: Location Dictates Function

Abstract

Stimulator of interferon response cGAMP interactor 1 (STING1), also known as TMEM173, is an immune adaptor protein that governs signal crosstalk that is implicated in many physiological and pathological processes. Although it has been established that STING1 traffics from the endoplasmic reticulum (ER) to Golgi apparatus (Golgi) upon DNA-triggered activation, emerging evidence reveals that STING1 can be transported to different organelles, which dictate its immune-dependent (e.g., the production of type I interferons and pro-inflammatory cytokines) and -independent (e.g., the activation of autophagy and cell death) functions. In this brief review, we outline the roles of STING1 in different organelles (including the ER, ER-Golgi intermediate compartment, Golgi, mitochondria, endosomes, lysosomes, and nucleus) and discuss the potential relevance of these roles to diseases and pharmacological interventions.

Induction of Inflammation Disrupts the Negative Interplay between STING and S1P Axis That Is Observed during Physiological Conditions in the Lung

“…Although it has been established that STING traffics from the endoplasmic reticulum (ER) to the Golgi apparatus upon DNA derivatives recognition, emerging evidence reveals that STING can be transported to different organelles. This dictates its immune-dependent (e.g., the production of type I IFN and pro-inflammatory cytokines) and/or immune-independent (e.g., the activation of autophagy, ER stress, cell death, and lipid metabolism) physiological functions [2]. Upon activation and translocation, STING binds and activates TANK-binding kinase 1 (TBK1), ensuing in IFN regulatory factor 3 (IRF3) recruitment and phosphorylation.…”

The STING1-MYD88 complex drives ACOD1/IRG1 expression and function in lethal innate immunity

“…Stimulator of interferon response CGAMP interactor 1 (STING1, also known as TMEM173 or STING) is a well-known regulator of the cyclic GMP-AMP synthase (CGAS)-dependent DNA sensor pathway, which drives antiviral immunity by producing type I interferons (IFNs) ( Ishikawa and Barber, 2008 ; Ishikawa et al., 2009 ; Sun et al., 2009 ; Zhong et al., 2008 ). Increasing evidence highlights that a dysfunctional STING1 pathway is implicated in sterile inflammation and infection ( Barber, 2015 ; Motwani et al., 2019 ; Zhang et al., 2022a ). We and others have recently demonstrated that excessive activation of the STING1 pathway contributes to cytokine storms, systemic coagulation, and multiple organ failure in experimental models of sepsis ( Ge et al., 2019 ; Heipertz et al., 2017 ; Hu et al., 2019 ; Kang et al., 2017 ; Ning et al., 2020 ; Wu et al., 2020 ).…”