# Cellular mechanisms of bioenergetic plasticity

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2024 · $13,074

## Abstract

ABSTRACT (PARENT GRANT)
The long-term goal of our research program is to understand how cells fine-tune their metabolic programs to
meet their ever-changing energetic needs. Many cell types in the body, from muscle fibers to neurons, have
evolved unique metabolic programs that are essential for survival and proper function. Even within a single cell,
specific processes are energetically coupled to mitochondria or the glycolytic machinery for specialized metabolic
support. However, the underlying molecular basis of metabolic plasticity and its relationship to cellular function
are poorly understood. Understanding the mechanisms of metabolic regulation is highly relevant to many disease
states, including diabetes, myopathies, and Leigh syndrome, where metabolic dysfunction is heavily implicated.
In eukaryotic cells, energy, in the form of ATP molecules is primarily produced by glycolysis and mitochondrial
oxidative phosphorylation. My laboratory combines optical imaging of biosensors in live cells with genomics and
transcriptomic analysis to investigate metabolic regulation in cellular compartments. With these tools, we have
been able to discover novel pathways for stimulation of mitochondrial and glycolytic ATP production in active
neurons during electrical activity. We now seek to understand how energy metabolism is locally regulated
in subcellular compartments and uncover metabolic specialization of functionally distinct neuronal
types. To carry out this work, we plan to utilize our strength in cellular imaging of metabolic function along with
new technological advances to: (1) determine how subcellular organization of the glycolytic machinery regulates
synaptic vesicle endocytosis, and (2) elucidate molecular mechanisms of metabolic specialization using the
available transcriptional profiles of neuronal subtypes. Our study will shed light on both local and global
mechanisms of metabolic plasticity at the subcellular level and across cell types. As such, our findings will be
broadly relevant to the scientific community studying cellular metabolism and its implications in disease states.

## Key facts

- **NIH application ID:** 10938150
- **Project number:** 3R35GM147222-02S1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Ghazaleh Ashrafi
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $13,074
- **Award type:** 3
- **Project period:** 2022-08-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10938150

## Citation

> US National Institutes of Health, RePORTER application 10938150, Cellular mechanisms of bioenergetic plasticity (3R35GM147222-02S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10938150. Licensed CC0.

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