# Cellular basis of mtDNA transmission.

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $302,225

## Abstract

PROJECT SUMMARY
Mitochondria are endosymbiotic organelles that possess a residual genome (mtDNA)
encoding a handful of proteins and ribosomal and transfer RNAs essential for their
functions. Human cells possess 100-1000s of mtDNAs, actively condensed into
nucleoids - protein-DNA structures that are the cellular unit of mtDNA inheritance –
distributed within dynamic mitochondria “syncytia”. Although the molecular players
involved in mtDNA replication and packaging have been described, much less is
understood about how at the cellular level nucleoids are distributed within mammalian
cells to meet the needs for mitochondrial function, for example, how they are selected for
mtDNA replication and how the cellular copy number of mtDNA is controlled. We
discovered that in human cells, nucleoids engaged in mtDNA replication are spatially
linked to a small subset of ER-mitochondria contact sites destined for mitochondrial
division and motility. We found that the successive events of mtDNA replication,
mitochondrial division and mitochondrial motility function together in a pathway that
preferentially distributes nascent mtDNA in cells, which we term ER-linked mtDNA
transmission. In this grant, we explore the underlying mechanisms of this ER-linked
mtDNA transmission pathway by addressing the cell biology and behavior of the
mammalian nucleoid. New information in this understudied area of cell biology will more
accurately reveal the etiology of human metabolic diseases caused by mutations in
mtDNA and in nuclear genes that affect mtDNA maintenance and in aging and
neurodegenerative disorders, which are also linked to defective mtDNA maintenance
and mitochondrial and ER dysfunction.

## Key facts

- **NIH application ID:** 9997961
- **Project number:** 5R01GM126081-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Jodi M. Nunnari
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $302,225
- **Award type:** 5
- **Project period:** 2017-09-15 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997961

## Citation

> US National Institutes of Health, RePORTER application 9997961, Cellular basis of mtDNA transmission. (5R01GM126081-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9997961. Licensed CC0.

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