# Regulation of mitochondrial homeostasis through retrograde signaling

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $438,303

## Abstract

PROJECT SUMMARY / ABSTRACT
Because the majority of mitochondrial proteins are encoded in the nuclear genome,
mitochondrial biogenesis and maintenance of mitochondrial homeostasis ultimately
depend on nuclear transcription being regulated in response to mitochondrial damage
and to changes in cell metabolism or nutrients availability. However, the pathways
controlling mitochondria-to-nucleus communication in mammalian cells are still largely
unknown. Here, we propose to investigate the hypothesis that the transcriptional
cofactor GPS2 regulates mitochondrial homeostasis as a direct mediator of
mitochondrial retrograde signaling in mammalian cells with the following Aims: i)
Characterize the role of GPS2 in promoting transcriptional activation of nuclear-encoded
mitochondrial genes; ii) Dissect the regulation of GPS2 shuttling between mitochondria
and nucleus and define the gene programs regulated upon translocation; iii) Elucidate
the role of GPS2 retrograde translocation in regulating mitochondrial homeostasis. To
achieve these goals, we will use a combination of biochemical techniques, genome wide
ChIPseq/RNAseq experiments and open-ended proteomic approaches to dissect the
molecular mechanism underlying GPS2-mediated regulation of mitochondrial gene
expression in the nucleus and elucidate the regulatory strategies that control GPS2
retrograde translocation both in conditions of mitochondrial stress and during the
differentiation of specialized cell lineages. Overall, successful completion of the studies
outlined in this application will: 1) identify a novel player in the regulation of mitochondrial
gene expression and elucidate the molecular mechanism of its transcriptional activity, 2)
dissect the first direct pathway of mitochondrial retrograde signaling in mammalian cells,
and 3) reveal an unexpected regulatory strategy for integrating stress and metabolic
signaling within the cell through inhibition of non-proteolytic ubiquitination.

## Key facts

- **NIH application ID:** 10133090
- **Project number:** 5R01GM127625-04
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** VALENTINA PERISSI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $438,303
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133090

## Citation

> US National Institutes of Health, RePORTER application 10133090, Regulation of mitochondrial homeostasis through retrograde signaling (5R01GM127625-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10133090. Licensed CC0.

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