# Molecular mechanisms of mtDNA inheritance

> **NIH NIH R00** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $249,000

## Abstract

Project Summary
Mitochondrial DNA (mtDNA) encodes RNAs and proteins critical for cell function. However, pathways that
control mtDNA segregation and copynumber in mammalian cells are not well understood. The goals of this
work are to identify and characterize the unknown protein machinery that segregates replicating mtDNAs into
discrete nucleoid structures at ER-mitochondria contact sites and to describe the mechanisms and pathways
that regulate mtDNA copy number. The proposed experiments will provide fundamental insight into the
mechanism of mtDNA segregation and copynumber control, and how those processes are regulated,
potentially leading to the discovery and characterization of novel pathways that regulate the inheritance of
mtDNA disease haplotypes. In Aim 1, cutting-edge live-cell microscopy, proteomics, and high-throughput
sequencing technologies will be employed to dissect the molecular functions of mtDNA segrosome candidate
proteins identified in preliminary experiments. Aim 2 will address which cellular pathways are critical to
regulation of mtDNA copy number in human cells. This will be accomplished by systematic genome-wide
screens for modulators of mtDNA depletion recovery, single-cell RNA sequencing to cluster genes by their
transcriptional responses to mtDNA loss, and the characterization of candidate mtDNA copynumber effector
proteins in human cells depleted of mtDNA. These experiments will provide fundamental insight into the
mechanism of mtDNA segregation and copynumber control, and how those processes are regulated,
potentially leading to the discovery and characterization of novel pathways that regulate the inheritance of
mtDNA disease haplotypes.

## Key facts

- **NIH application ID:** 10124408
- **Project number:** 5R00GM129456-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Samantha C Lewis
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2018-08-07 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10124408

## Citation

> US National Institutes of Health, RePORTER application 10124408, Molecular mechanisms of mtDNA inheritance (5R00GM129456-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10124408. Licensed CC0.

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