# Global Intracellular Responses to Mitophagy

> **NIH NIH R35** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2022 · $386,751

## Abstract

PROJECT SUMMARY
Mitochondria perform oxidative phosphorylation to generate ATP for a majority of the cells in the body. The
accumulation of damaged or dysfunctional mitochondria contribute to a wide range of human diseases.
Mitophagy is a quality control process that eliminates and recycles damaged mitochondria to prevent their
accumulation. A majority of studies focus on how mitophagy defects affect post-mitotic cells because the first
identified autosomal recessive mutations in mitophagy genes caused neurodegenerative diseases such as
Parkinson’s. However, it is now clear that many other cell types have high levels of mitophagic activity; yet, we
do not understand the importance or impact of mitophagy in these contexts. For example, stem cells display high
levels of mitophagy, divide continuously throughout their lifespan, and possibly use mitophagy as a mechanism
to ensure daughter cells receive healthy mitochondria. Towards this goal, our findings support that mitophagy
and cell division are intimately linked by a required interorganelle signaling kinase that translocates to either
mitochondria or centrosomes to activate either cell process. To build upon this work within the next five years,
this proposal will use live imaging, genetic drosophila screens, cell biology and biochemical approaches,
transgenic mouse models, and primary stem cells to answer the following questions: 1) Do defects in mitophagy
affect stem cell division and mitochondrial inheritance? 2) Can we identify other mitophagy proteins/genes that
influence cell division? 3) Does the type of interorganelle signaling that connects mitophagy and cell division
control other cellular processes when dictated by its subcellular localization? The broad implications of this work
will elucidate why mitophagy genes are mutated in other complex diseases such as cancer, provide insight into
how mitochondrial dysfunction affects stem cells contributing to neurodevelopmental and cognitive disorders,
and define fundamental signaling interactions between organelles to deepen our understanding of how cells
globally respond to dysfunctional mitochondria.

## Key facts

- **NIH application ID:** 10469574
- **Project number:** 5R35GM142368-02
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Alicia M Pickrell
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $386,751
- **Award type:** 5
- **Project period:** 2021-08-13 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469574

## Citation

> US National Institutes of Health, RePORTER application 10469574, Global Intracellular Responses to Mitophagy (5R35GM142368-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10469574. Licensed CC0.

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