# Elucidating the structural basis of mitochondrial outer membrane permeabilization in apoptosis

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 2022 · $321,300

## Abstract

Abstract
Mitochondrial apoptosis is a stress-triggered cell death pathway implicated in health and disease. This
pathway is readily blocked in cancer. Mitochondrial poration is at the heart of mitochondrial apoptosis being
regulated by the BCL-2 proteins. This process regulates the release from mitochondria of prodeath factors that
activate the caspase cascade which dismantles apoptotic cells. Mitochondrial poration is executed by the
BCL-2 protein BAK. Here we propose to delineate the mechanism of mitochondrial poration by BAK, which is
elusively defined and controversial. In particular, we propose to elucidate 1) the mechanism of BAK activation,
2) BAK association with and poration of membranes, and 3) BAK recognition and sequestration by prosurvival
BCL-2 proteins. To accomplish these aims we will use a multi-pronged approach including high-resolution
structural biology, biophysics, biochemistry, and cell biology to generate a complete picture of mitochondrial
poration by BAK. Upon successful completion we will redefine our mechanistic understanding of this process,
and we will reveal innovative ways to target apoptosis in pathophysiology.

## Key facts

- **NIH application ID:** 10670577
- **Project number:** 7R01GM129470-03
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** Tudor Moldoveanu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $321,300
- **Award type:** 7
- **Project period:** 2020-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10670577

## Citation

> US National Institutes of Health, RePORTER application 10670577, Elucidating the structural basis of mitochondrial outer membrane permeabilization in apoptosis (7R01GM129470-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10670577. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*