# Spatial Organization of the Mitochondrial Inner Membrane

> **NIH NIH R35** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $74,460

## Abstract

Project Summary
Mitochondria are double-membrane bound organelles that perform many crucial cellular functions, including
nucleotide and amino acid metabolism, cellular phospholipid and ion homeostasis, and their most notorious
function, generation of cellular energy via oxidative phosphorylation. Mitochondrial form and function are tightly
linked. The ability of the organelle to efficiently perform respiration depends on the correct spatial organization
of the mitochondrial inner membrane into elaborately shaped morphological domains, including cristae, the
hallmark of the organelle. Cristae morphology defects lead to reduced cellular respiration and is a phenotypic
consequence of a number of diseases, including neurodegenerative disorders such as Alzheimer’s and
Parkinson’s Disease. Despite their importance, we have minimal mechanistic understanding of how cristae are
formed and organized within the organelle. Recently, the Mitochondrial Contact Site and Cristae Organizing
System (MICOS) complex was identified as a master regulator of spatial organization of mitochondria. I
previously determined that MICOS is organized into two non-redundant subcomplexes that independently
assemble and localize to cristae junctions, a key structural element of the mitochondrial inner membrane.
Despite our progress, we have minimal mechanistic understanding of how MICOS contributes to the number,
position, and morphogenesis of cristae membranes. In the next five years, our goal is to address these deficits
by exploring the molecular basis of MICOS function in yeast cells and, using candidate and forward genetic
strategies, determine how MICOS is regulated to fine tune cristae architecture in human cells. This work will
lead to insight into the spatial organization of mitochondria and the form-function relationship of the organelle,
provide the basis for the future development of my research program, and give us molecular insight into the
disorganization of mitochondrial membranes that occurs as a consequence of a number of human diseases.

## Key facts

- **NIH application ID:** 10467263
- **Project number:** 3R35GM137894-02S1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Jonathan R. Friedman
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $74,460
- **Award type:** 3
- **Project period:** 2020-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10467263

## Citation

> US National Institutes of Health, RePORTER application 10467263, Spatial Organization of the Mitochondrial Inner Membrane (3R35GM137894-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10467263. Licensed CC0.

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