# Structure, Function, and Mechanism of a Mitochondrial Chaperone

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $460,421

## Abstract

SUMMARY
Mitochondria function as the powerhouses of the cell and are essential to cellular and organismal health.
Conversely, mitochondrial degeneration and dysfunction are hallmarks of human diseases including
developmental and metabolic disorders, type 2 diabetes, Alzheimer's disease, Parkinson's disease, Huntington's
disease, cancer, atherosclerosis, and cardiovascular diseases. Consequently, several surveillance strategies
have evolved consisting of molecular chaperones and energy-dependent proteases that protect mitochondria
from damage. Mitochondria possess a representative member of every stress-inducible chaperone family; thus,
providing a paradigm to elucidate the function of the ensemble of molecular chaperones in proteostasis
maintenance. It is widely appreciated that molecular chaperones provide the first line of defense against protein
misfolding by promoting the correct folding and preventing aberrant folding and aggregation. Mitochondrial
chaperones are also widely expressed in most tumor cell types, including colorectal, breast, prostate, and
ovarian cancer, which have the highest mortality rates, indicating a central role of mitochondrial chaperones in
the immortalization of cancer cells and underscoring their significance as promising anti-cancer drug targets.
The broad and long-term research objective is to provide a molecular understanding how mitochondrial
chaperones maintain proteostasis under physiological conditions and how their function is modulated in
pathological states. Specifically, we will focus on the structural analysis of a novel ATP-dependent mitochondrial
chaperone using X-ray crystallography and cryoEM, determine its protein interactome using functional
proteomics, and use a structure-guided mutagenesis approach to elucidate its biological function in vitro and in
living cells. Addressing an important biomedical problem using a multi-pronged approach at different resolution
and time scale underscores the significance and impact of the proposed research.

## Key facts

- **NIH application ID:** 10493261
- **Project number:** 5R01GM142143-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Francis T.F. Tsai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $460,421
- **Award type:** 5
- **Project period:** 2021-09-30 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10493261

## Citation

> US National Institutes of Health, RePORTER application 10493261, Structure, Function, and Mechanism of a Mitochondrial Chaperone (5R01GM142143-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10493261. Licensed CC0.

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