# Molecular basis and cellular roles of mitochondria-ER contact sites

> **NIH NIH R37** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $383,417

## Abstract

Mitochondria perform fundamental functions in eukaryolic cells, including ATP production via respiration
and cellular ion and phospholipid homeostasis. They also serve as platforms to integrate signaling
pathways such as cell death and innate immunity. Mitochondrial functions are tightly linked to
mitochondrial form, established through separate, but somehow coordinated machines that control
dynamics, positioning, motility and mitochondrial DNA (mtDNA) transmission. The endoplasmic reticulum
(ER) has emerged as an integral and pervasive player in the regulation of mitochondrial form and
function. The ER exerts its role through contacts with mitochondria, which our data indicate create
specialized microdomains that recruit and/or modulate resident effectors to control and integrate
mitochondrial status with other organelles and signaling pathways. In this MERIT award, we are exploring
the fundamental properties and functions of membrane contact sites (MCS), with a particular emphasis on
ER-mitochondria contact sites using budding yeast, where they are the best characterized. We have
shown that one MCS, ERM ES, serves as a systems regulator to create a cellular pathway for the
transmission of mtDNA and that this function of ER-mitochondria contacts is fundamentally conserved in
human cells. We will extend our findings to explore the molecular basis of the action of the ERM ES
complex in mtDNA transmission. We also discovered a family of conserved contact site proteins that
serve to transport sterols and regulate Ca2+ homeostasis at ER-plasma membrane,
ER-vacuole/lysosome and ER-mitochondria contacts in yeast and human cells. We will utilize high
resolution yeast genetics to discover the unknown but fundamental role of sterol transport between the ER
and mitochondria. New information in this area of cell biology will provide insight into the general
architecture and roles of ER MCSs and their regulation of mitochondrial function and cellular homeostasis
to more accurately reveal role of mitochondria in human diseases.

## Key facts

- **NIH application ID:** 9829706
- **Project number:** 4R37GM097432-10
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Jodi M. Nunnari
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $383,417
- **Award type:** 4C
- **Project period:** 2011-09-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9829706

## Citation

> US National Institutes of Health, RePORTER application 9829706, Molecular basis and cellular roles of mitochondria-ER contact sites (4R37GM097432-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9829706. Licensed CC0.

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