# Mitonuclear coordination of gene expression across complex cellular states using mitoribosome profiling

> **NIH NIH F32** · HARVARD MEDICAL SCHOOL · 2022 · $69,802

## Abstract

PROJECT SUMMARY / ABSTRACT
Coordination of gene expression across nuclear and mitochondrial genomes within a cell is crucial for the
correct assembly of oxidative phosphorylation (OXPHOS) complexes that make up the electron transport chain
and enable aerobic life. This mitonuclear balance must be tightly orchestrated by molecular players across
cellular compartments and critically must adapt to a dynamic cellular milieu. Balanced gene expression across
these genomes poses a unique challenge when we consider complex cellular states, for example aged cells
that must deal with declining proteomes among other insults or long-lived, morphologically complex cells like
neurons where this coordination could rapidly breakdown. Failure to maintain proper mitonuclear balance and
the resulting mitochondrial dysfunction is implicated in a myriad of human diseases, including
neurodegenerative diseases and cancer, as well as the aging process itself.
Our lab has previously demonstrated that mitochondrial and nuclear genomes regulate coordinated gene
expression programs on the translational but not transcriptional level for dual-origin OXPHOS genes required
to build respiratory complexes during mitochondrial biogenesis. These studies utilized simultaneous cytosolic
and mitochondrial ribosome profiling techniques, but to date have only been performed in healthy mid-log
phase yeast. Our long-term objectives are now to understand how mitochondrial genomes are regulated
across diverse cellular states and biological contexts. Our specific aims for this proposal that will help us attain
these objectives are twofold: (1) to determine the effects of a deteriorating cellular environment during a cell’s
lifespan on mitochondrial gene expression and mitonuclear coordination using replicatively-aged yeast and (2)
determine how post-mitotic neurons which must have different mitochondrial demands in the soma compared
to distal neurites can maintain proper mitonuclear coordination and appropriately regulate mitochondrial gene
expression over the lifespan of this long-lived and morphologically complex cell. In summary this proposed
research will advance our knowledge of mitochondrial gene regulation and mitochondrial biology in cellular
states with relevance to human disease and aging.

## Key facts

- **NIH application ID:** 10475110
- **Project number:** 5F32GM139244-03
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Nicholas John Kramer
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $69,802
- **Award type:** 5
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475110

## Citation

> US National Institutes of Health, RePORTER application 10475110, Mitonuclear coordination of gene expression across complex cellular states using mitoribosome profiling (5F32GM139244-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10475110. Licensed CC0.

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