Honors Theses
Date of Award
Spring 5-8-2026
Document Type
Undergraduate Thesis
Department
Chemistry and Biochemistry
First Advisor
Mika Jekabsons
Second Advisor
Bradley Jones
Third Advisor
Karel Alcedo
Relational Format
Thesis
Abstract
Voltage-dependent anion channels (VDACs) are central to mitochondrial function by mediating metabolite diffusion across the mitochondrial outer membrane (MOM). Two isoforms, VDACs 1 and 2, are also implicated in apoptosis based on interactions with Bcl-2 family proteins that control this process, including Bax and Bcl-xL. Activation of the pro-apoptotic protein Bax by interaction with ‘BH3-only’ proteins, such as Bim or Bid, induces MOM permeabilization to signal apoptosis, yet accumulating evidence indicates VDACs 1 and 2 may also affect Bax. We discovered that the VDAC N-terminal domains contain high sequence similarity to the conserved BH3 domains within Bcl-2 family members that are necessary to control apoptosis. Based on this, we hypothesized that these BH3-like domains interact with the hydrophobic groove of Bax to promote its activation. Recombinant Bax activation was assessed by measuring 6A7 epitope exposure following treatment with VDAC peptides using immunoprecipitation and Western blotting. Both VDAC1 and VDAC2 N-terminal peptides promoted Bax activation, while mutation of four conserved hydrophobic residues (H1 – H4) abolished this effect. Residue pairs H1/H3 and H2/H4 were identified as particularly critical for Bax activation. Although the in vitro conditions cannot be extrapolated in vivo, the results implicate VDAC BH3-like domains as direct regulators of Bax and define key residues involved in this interaction.
Recommended Citation
Peters, Autumn A., "Bax Activation through the N-terminal BH3-like Domains of VDAC1 and VDAC2" (2026). Honors Theses. 3580.
https://egrove.olemiss.edu/hon_thesis/3580
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