# Mechanisms by which Bok binds to IP3Rs and regulates mitochondrial dynamics

> **NIH NIH F30** · UPSTATE MEDICAL UNIVERSITY · 2021 · $51,036

## Abstract

PROJECT SUMMARY
The Bcl-2 protein family is a group of proteins that plays an important role in intrinsic apoptosis and
includes the protein Bok. While many members of the Bcl-2 protein family have been thoroughly
studied, Bok is a very poorly understood protein, with pro-, anti-, and non-apoptotic properties reported.
Our lab has shown previously that Bok is constitutively bound to inositol 1,4,5-trisphosphate receptors
(IP3Rs), which are tetrameric calcium channels found in the endoplasmic reticulum (ER) membrane of
mammalian cells. While other Bcl-2 protein family members have been reported to interact with IP3Rs,
the Bok-IP3R interaction is much more efficient, with essentially all Bok bound to IP3Rs. We have shown
that Bok interacts with IP3Rs in all tissues, including cerebral cortex and hippocampus. Additionally, we
have discovered that Bok protects IP3Rs from proteolytic cleavage, and in the absence of IP3Rs, Bok
is ubiquitinated and rapidly degraded by the proteasome. Recent data has shown that Bok promotes
mitochondrial fusion, and Bok knock-out mouse embryonic fibroblast cells have more fragmented
mitochondria compared to control cells. Since Bok is expressed highly in hippocampal neurons, and
mitochondrial dysfunction can often lead to neurodegenerative disease, it is possible that Bok plays a
role in the development of neurodegenerative disease. Therefore, the current aims of this study are 1)
to determine how ER-bound Bok promotes mitochondrial fusion activity and 2) to define the exact
nature of the Bok-IP3R binding interface. Results from these aims will fill our current gaps in knowledge
regarding Bok’s role in the cell and the Bok-IP3R interaction, and can contribute to our overall
knowledge of the various functions of the Bcl-2 protein family.

## Key facts

- **NIH application ID:** 10224261
- **Project number:** 5F30GM134638-03
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** Laura Szczesniak
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $51,036
- **Award type:** 5
- **Project period:** 2019-08-03 → 2022-08-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10224261

## Citation

> US National Institutes of Health, RePORTER application 10224261, Mechanisms by which Bok binds to IP3Rs and regulates mitochondrial dynamics (5F30GM134638-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10224261. Licensed CC0.

---

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