# Systems analysis of mitochondrial genome maintenance in physiological context

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $387,069

## Abstract

Project Description/Summary
Mitochondrial DNA (mtDNA) encodes RNAs and proteins critical for cell function. However, the
pathways that regulate mtDNA synthesis and segregation in animal cells are not well
understood. The goals of this work are to identify the protein components of mitochondrial DNA
nucleoid complexes, to investigate how mitochondrial replication and dynamics are coordinated
to homeostatically maintain mtDNA nucleoid segregation and abundance, and to probe the
mechanisms underlying selection against mutant mtDNAs in somatic cells. These experiments
will provide fundamental insights into the maintenance of the essential mitochondrial
chromosome in animal cells and how maintenance processes are regulated, potentially leading
to the discovery and characterization of novel pathways that regulate the inheritance of mtDNA
disease alleles. We will employ cutting-edge microscopy of living cells and whole animals,
proteomics, and single cell transcriptional analyses to interrogate the molecular functions of
candidate proteins implicated in the maintenance of mtDNA integrity. These experiments will
reconcile inconsistencies in the mitochondrial biology literature, provide fundamental insight into
the mechanisms of mtDNA copy number control, and identify novel pathways that regulate the
tissue-specific manifestations of mitochondrial dysfunction.

## Key facts

- **NIH application ID:** 10908559
- **Project number:** 5R35GM147218-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Samantha C Lewis
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $387,069
- **Award type:** 5
- **Project period:** 2022-09-15 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908559

## Citation

> US National Institutes of Health, RePORTER application 10908559, Systems analysis of mitochondrial genome maintenance in physiological context (5R35GM147218-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10908559. Licensed CC0.

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