# Mitochondrial Amyloid Beta accumulation via non-canonical receptor Tom22

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2020 · $415,555

## Abstract

Compelling evidence has suggested that mitochondrial dysfunction is an early event in Alzheimer’s Disease
(AD) pathophysiology. This mitochondrial dysfunction is closely related to the elevated level of intracellular Aβ,
which appears to be accumulated within mitochondria in the brains of both Alzheimer’s patients and mouse
models. How mitochondria actively accumulate Aβ is not clear, and thus represents a large gap of knowledge
in the field. We aim to understand the very first step of this accumulation process by studying the detailed
molecular mechanism of substrate/receptor interaction. We have identified that Aβ is recognized by a non-canonical receptor, Tom22, within the mitochondrial protein import machinery. In this proposal, we expect to
perform two related but independent specific aims to reach that goal. 1). We will characterize the interaction
between Aβ and Tom22 receptor in details, by biophysical, biochemical and cell biology tools; 2). We expect to
determine three dimensional atomic structures of Tom22 and Tom22/Aβ complex. The functional and structural
information gained here are expected to reveal detailed molecular mechanism underlining the detrimental
process of mitochondrial uptake of Aβ peptides, and thus provide novel models to screen molecules that are
capable of disrupting the specific Tom22/Aβ interaction. Thus, the outcome of this proposal is expected to
have important positive impact in treating mitochondrial dysfunction caused by Aβ in AD.

## Key facts

- **NIH application ID:** 9976158
- **Project number:** 1R21AG064572-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Hongjin Zheng
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $415,555
- **Award type:** 1
- **Project period:** 2020-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976158

## Citation

> US National Institutes of Health, RePORTER application 9976158, Mitochondrial Amyloid Beta accumulation via non-canonical receptor Tom22 (1R21AG064572-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9976158. Licensed CC0.

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