Work

Identification of Inhibitors Against BAK Pore Formation using an Improved in vitro Assay System

Year: 2014

Type: article

Abstract: The pro-apoptotic BCL-2 family protein BID activates BAK and/or BAX, which form oligomeric pores in the mitochondrial outer membrane. This results in the release of cytochrome c into the cytoplasm, initiating the apoptotic cascade. Here, we utilized liposomes encapsulating sulfo-rhodamine at a controlled temperature to improve upon a previously reported assay system with enhanced sensitivity and specificity for measuring membrane permeabilization by BID-dependent BAK activation. BAK activation was inhibited by BCL- $X_L$ protein but not by a mutant protein with impaired anti-apoptotic activity. With the assay system, we screened a chemical library and identified several compounds including trifluoperazine, a mitochondrial apoptosis-induced channel blocker. It inhibited BAK activation by direct binding to BAK and blocking the oligomerization of BAK.

Source: Bulletin of the Korean Chemical Society

DOI: 10.5012/bkcs.2014.35.2.419

Authors: Seong-Soo Song, Won-Kyu Lee, Sreevidya Aluvila, Kyoung Joon Oh, Yeon Gyu Yu

Institutions: Kookmin University, Rosalind Franklin University of Medicine and Science

Language: English

Topic: Cell death mechanisms and regulation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

OpenAlex ID: W2006691778