BAX inhibitor‐1: between stress and survival

Abstract

Cellular gatekeepers are essential to maintain order within a cell and anticipate signals of stress to promote survival. BCL2 associated X, apoptosis regulator (BAX) inhibitor‐1 (BI‐1), also named transmembrane BAX inhibitor motif containing‐6, is a highly conserved endoplasmic reticulum (ER) transmembrane protein. Originally identified as an inhibitor of BAX‐induced apoptosis, its pro‐survival properties have been expanded to include functions targeted against ER stress, calcium imbalance, reactive oxygen species accumulation, and metabolic dysregulation. Nevertheless, the structural biology and biochemical mechanism of action of BI‐1 are still under debate. BI‐1 has been implicated in several diseases, including chronic liver disease, diabetes, ischemia/reperfusion injury, neurodegeneration, and cancer. While most studies have demonstrated a beneficial role for BI‐1 in the ubiquitous maintenance of cellular homeostasis, its expression in cancer cells seems most often to contribute to tumorigenesis and metastasis. Here, we summarize what is known about BI‐1 and encourage future studies on BI‐1's contribution to cellular life and death decisions to advocate its potential as a target for drug development and other therapeutic strategies.

RETRACTED: Exosomes From Cancer-Associated Mesenchymal Stem Cells Transmit TMBIM6 to Promote the Malignant Behavior of Hepatocellular Carcinoma via Activating PI3K/AKT Pathway

“…TMBIM6, also known as Bax inhibitor-1, is an inhibitor of Bax-mediated apoptosis ( 45 ). In cancers, TMBIM6 is regarded as a promoter of cancer progression.…”

Integrating Statistical and Machine-Learning Approach for Meta-Analysis of Bisphenol A-Exposure Datasets Reveals Effects on Mouse Gene Expression within Pathways of Apoptosis and Cell Survival

“…Furthermore, the protein of another gene recovered in the study, Apaf1 , acts downstream of Bax, and, along with Caspase-9, forms an apoptosome to induce apoptosis ( Figure 3 ) [ 37 ]. Interestingly, we also showed that Tmbim6 transcript levels are affected by BPA, and Tmbim6 was shown to inhibit Bax-induced apoptosis ( Figure 3 ) [ 38 ].…”

Genome‐wide transcriptome analysis identifies novel dysregulated genes implicated in Alzheimer's pathology

“…TMBIM6 is highly conserved and ubiquitously expressed in humans, and has been shown to play a role in numerous cellular pathways including ER stress, calcium imbalance, reactive oxygen species accumulation, and metabolic dysregulation. More specifically, this protein is involved in cellular calcium and pH homeostasis by mediating Ca(2+) efflux from the ER, and functions to protect the cell from ER stress‐induced apoptotic cell death, although the exact molecular mechanism underlying this protein function is currently unclear 49‐51 . Altered TMBIM6 expression could dysregulate cellular response to stress, with interesting implications for AD susceptibility and progression.…”