# Molecular Dissection of Mitochondria-Organelle Interactions

> **NIH NIH DP2** · UNIVERSITY OF WASHINGTON · 2020 · $2,332,500

## Abstract

PROJECT SUMMARY/ ABSTRACT
Mitochondria are multi-functional organelles that play central roles in metabolism, protein homeostasis, calcium
signaling, immunity, and cell death. Perturbation of these mitochondrial functions is an underlying feature of
several common diseases and physiological conditions such as cancer, neurodegenerative diseases and
aging. Interaction of mitochondria with other organelles plays a pivotal role in regulation of mitochondrial
functions. However these mitochondria-organelle interactions remain poorly understood, partly due to lack of
methods that enable isolation and characterization of mitochondria that associate with different organelles.
This also hinders investigation of mitochondria-organelle interactions in diseases and their contribution to
disease pathogenesis. The goal of this proposal is to overcome this technical challenge in order to investigate
the mechanisms of mitochondria regulation through organelle interactions in cell lines and cellular models of
mitochondrial diseases. Here, I propose the development of an innovative biochemical workflow that will allow
differential tagging and rapid isolation of mitochondria based on their cellular location and organellar
interactions. Using this method, we will first characterize the proteome and metabolite composition of
mitochondria that are in close proximity to four organelles and the plasma membrane. Next, we will investigate
whether specific metabolites and protein modifications regulate mitochondrial functions at organelle contact
sites. We will also determine how mitochondria- organelle interactions are altered in cellular models of
mitochondrial disease and whether these interactions can be targeted for therapeutic gain. These experiments
will be the first comprehensive biochemical analysis of mitochondria-organelle interactions in healthy cells and
cells with mitochondrial dysfunction. Our results will lead to identification of signals that originate from different
cellular structures to regulate mitochondrial functions and will elucidate their mechanisms. In addition,
investigation of mitochondria-organelle interactions in cells with mitochondrial dysfunction has the potential to
transform our understanding of mechanisms of mitochondrial diseases, which will lead to novel treatment
approaches. The methods developed can easily be applied to investigate other inter-organellar interactions to
reveal their mediators and mechanisms at unprecedented biochemical detail.

## Key facts

- **NIH application ID:** 10000604
- **Project number:** 1DP2ES032761-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Yasemin S Sancak
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,332,500
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000604

## Citation

> US National Institutes of Health, RePORTER application 10000604, Molecular Dissection of Mitochondria-Organelle Interactions (1DP2ES032761-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10000604. Licensed CC0.

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