Interactome analysis identifies the role of BZW2 in promoting endoplasmic reticulum-mitochondrial contact and mitochondrial metabolism

Mol Cell Proteomics. 2023 Dec 26:100709. doi: 10.1016/j.mcpro.2023.100709. Online ahead of print.ABSTRACTUnderstanding the molecular functions of less-studied proteins is an important task of life science research. Despite reports of BZW2 (Basic leucine zipper and W2 domain-containing protein 2) promoting cancer progression first emerging in 2017, little is known about its molecular function. Using a quantitative proteomic approach to identify its interacting proteins, we found that BZW2 interacts with both endoplasmic reticulum (ER) and mitochondrial proteins. We thus hypothesized that BZW2 localizes to and promotes the formation of ER-mitochondrial contact sites, and that such localization would promote calcium transport from ER to the mitochondria and promote ATP production. Indeed, we found that BZW2 localized to ER-mitochondria contact sites and that BZW2 knockdown decreased ER-mitochondrial contact, mitochondrial calcium levels, and ATP production. These findings provide key insights into molecular functions of BZW2, the potential role of BZW2 in cancer progression, and highlight the utility of interactome data in understanding the function of less-studied proteins.PMID:38154691 | DOI:10.1016/j.mcpro.2023.100709
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Source Type: research