TXNIP shuttling: missing link between oxidative stress and inflammasome activation

Narasaiah Kolliputi,Brenda Flam,Troy Lane,Richard Lockey

doi:10.3389/fphys.2013.00050

Abstract

OPINION article Front. Physiol., 21 March 2013Sec. Redox Physiology Volume 4 - 2013 | https://doi.org/10.3389/fphys.2013.00050

Highlights

Thioredoxin-interacting protein (TXNIP) has been linked to cell apoptosis and inflammation in a number of diseases, including type 2 diabetes (Shah et al, 2013), atherosclerosis (Berk, 2007), and myocardial ischemia (Yoshioka et al, 2012)
We interpret the facts on mitochondrial danger signaling: TXNIP’s role in the mitochondria, interactions with mitochondrial TRX2 and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome [an oligomeric complex activated by cellular infections or stress (Schroder and Tschopp, 2010)] signaling pathway not previously described
This study suggests that in the unstressed cell, TXNIP is bound to TRX1 and is inactive

Summary

Introduction

Thioredoxin-interacting protein (TXNIP) has been linked to cell apoptosis and inflammation in a number of diseases, including type 2 diabetes (Shah et al, 2013), atherosclerosis (Berk, 2007), and myocardial ischemia (Yoshioka et al, 2012). Mitochondrial thioredoxin, TRX2, like its cytoplasmic counterpart, TRX1, was found to regulate ROS and manage oxidative stress within mitochondria. We interpret the facts on mitochondrial danger signaling: TXNIP’s role in the mitochondria, interactions with mitochondrial TRX2 and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome [an oligomeric complex activated by cellular infections or stress (Schroder and Tschopp, 2010)] signaling pathway not previously described. ASK1 is usually bound to TRX2 under basal conditions, during stress and following TXNIP translocation to the mitochondria, ASK1-TRX2 binding is disrupted, triggering an apoptotic signal cascade.

Results

Conclusion