# Core D: Mitochondrial Structure & Function

> **NIH NIH P01** · UNIVERSITY OF WASHINGTON · 2020 · $242,780

## Abstract

CORE D: MITOCHONDRIAL STRUCTURE AND FUNCTION – SUMMARY/ABSTRACT
Recent findings of this PO1 revealed that treatment of aged mice with the mitochondria-targeted peptide (SS-
31) conferred rapid rejuvenation of mitochondrial bioenergetics, suggesting that SS-31 increases intrinsic
mitochondrial plasticity by increasing the capacity of the mitochondrial ETC to produce more ATP at times of
increased metabolic demands or decreased fuel supply. The mechanism by which SS-31 increases
mitochondrial plasticity is not completely understood, although recent work the Program Project and this Core
has now shown that these peptides target the inner mitochondrial membrane (IMM) because of their high
affinity for cardiolipin (CL). By modifying the interaction of CL and cytochrome c (cyt c), SS peptides protect the
hexacoordination of the heme Fe to optimize electron transport (ET) and minimize reactive oxygen species
(ROS) production. As a result, the SS peptides prevent oxidative stress in the mitochondrial inter membrane
space (IMS).
The goal of this Mitochondrial Structure and Function Core is to assist all Projects in the PO1 to demonstrate
that protection of mitochondrial structure by the SS peptides at the level of cristae architecture and cytochrome
c (cyt c) heme ligation can reduce mitochondrial aging in the heart, skeletal muscle and retina. The major
services provided by this Core include:
Aim 1 is to provide ultrastructural and protein characterization of age and high fat diet-mediated changes in
cristae architecture and composition, and protection by SS peptides.
Aim 2 is to provide characterization of age- and high fat diet-mediated changes in cyt c heme structure, and
protection by SS peptides. This will include providing the resources to assist all Projects in determining the
extent of oxidative stress in the mitochondrial IMS and working with Core B to obtain mass-spectrometry
confirmation of these oxidized proteins.
Aim 3 is to provide methods for studying mitochondrial electron transport chain structures. This will include
methods for identifying supercomplexes in mitochondria from retina, heart and skeletal muscles using 2-D
native blue gels/SDS gel electrophoresis and specific antibodies for the individual respiratory complex proteins.
In summary, this Core will determine if structural changes in mitochondrial cristae and cyt c heme ligation play
a role in the inhibition of ET and increase in ROS emission associated with aging. The SS peptides will provide
evidence to support the importance of repairing mitochondrial structure in order to restore cellular
bioenergetics and allow for repair of cellular structure and function.

## Key facts

- **NIH application ID:** 9918229
- **Project number:** 5P01AG001751-36
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** HAZEL H SZETO
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $242,780
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918229

## Citation

> US National Institutes of Health, RePORTER application 9918229, Core D: Mitochondrial Structure & Function (5P01AG001751-36). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/9918229. Licensed CC0.

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