# Regulation of mitochondrial morphology and functional versatility

> **NIH NIH R35** · NEW YORK UNIVERSITY · 2024 · $135,377

## Abstract

PROJECT SUMMARY
Eukaryotic cells sequester critical biochemical reactions into discrete membranous compartments, whereby
membrane dynamics driven by protein catalysts facilitate differentiation, communication, and spatial organization
of intracellular compartments. Within a cell, mitochondria are mainly organized into highly interconnected
networks, whose diverse functions are dependent on their complex structure and organization. In humans, OPA1
and MICOS are essential biomolecular machines that control not only the morphology of the mitochondrial
reticulum, but also the efficiency of many key mitochondrial processes, including oxidative phosphorylation,
metabolism, apoptosis, and mtDNA maintenance. The GTPase OPA1 is crucial for mitochondrial IM fusion and
regulating cristae dynamics, whereas the multi-component MICOS complex plays a dual role by shaping IM
cristae junctions and forming contact sites with the outer membrane. Characterizing how mitochondrial dynamics
are realized and regulated will be essential to deciphering the link between mitochondrial morphology and
function. Moreover, molecular abnormalities in mitochondrial dynamics result in aberrant mitochondrial structure,
impaired bioenergetics, severely reduced respiratory capacity, mtDNA instability, increased sensitivity to
apoptosis, and development of a wide variety of disease conditions, including neurodegenerative disorders,
diverse cancers, obesity, and cardiovascular diseases. Yet, the molecular mechanisms that alter mitochondrial
morphology and function remain incompletely understood. Here, using a combination of cellular and structural
analyses, we aim to develop a molecular understanding of mitochondrial dynamics that govern key physiological
processes in cells. We propose to determine the molecular mechanism of mitochondrial morphogenesis by
exploring the assembly mechanism of OPA1 and its interactions with the mitochondrial lipid cardiolipin (Aim 1).
We further propose to characterize the molecular details of multi-component MICOS complex and protein
dynamics that facilitate cristae formation and maintain the characteristic architecture of mitochondria (Aim 2).
Structural and functional studies of mitochondrial protein machines will provide a platform to identify the basis of
pathologies linked to human disease and age-related illness. Understanding the precise molecular mechanisms
of mitochondrial dynamics will increase the probability of success in developing new therapeutic interventions.

## Key facts

- **NIH application ID:** 11270149
- **Project number:** 7R35GM150942-03
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** HALIL AYDIN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $135,377
- **Award type:** 7
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11270149

## Citation

> US National Institutes of Health, RePORTER application 11270149, Regulation of mitochondrial morphology and functional versatility (7R35GM150942-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11270149. Licensed CC0.

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