# The role of the mitochondrial protein dimer CHCHD2/10 in health and disease

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $69,480

## Abstract

Skeletal muscle, heart, and brain are high-energy requiring tissues that are severely affected by mitochondrial
dysfunction. Recently a novel form of genetic disease affecting mitochondria has been associated with
mutations in a mitochondrial protein, CHCHD10 (D10), whose function is still largely unknown. Mutant D10
causes severe autosomal dominant mitochondrial diseases, with diverse phenotypic features, ranging from
myopathy and cardiomyopathy to motor neuron disease and frontotemporal dementia. The parent R01 that is
linked to this application for Diversity Supplement investigates the normal function of D10 and the mechanisms
underlying mitochondrial alterations in D10 S55L mutant mice. The supplement will support the work of Ms.
Nneka Southwell, a graduate student in the Neuroscience Program in Dr. Manfredi’s group. The focus of the
studies proposed in the supplement is on the metabolic rewiring involving 1C metabolism and nucleotide
imbalance, which she has observed in the D10 S55L mutant mouse, starting from the most affected tissue, the
heart, but also exploring metabolic alterations in various brain regions. The latter is highly innovative because
very little is known about mitochondrial metabolic stress responses in the CNS and it is possible that some
pathways are shared with heart and other tissues, while other could differ entirely. Maladaptive metabolic
rewiring is an emerging and fascinating field, which holds exciting promise to provide novel disease biomarkers
and therapeutic targets, not only for this mitochondrial disorder, but also for many other diseases that share
metabolic adaptation mechanisms. The studies proposed for this Diversity Supplement will provide ample
opportunities for Ms. Southwell to become an expert in metabolism and disease, an area of research that is
gaining tremendous momentum in the biomedical space, as a role for metabolic dysregulation is increasingly
being linked to a broad spectrum of diseases. The knowledge and technical skills that she will accumulate
working on this project will position her well to being able to develop her independent, cutting-edge research
on the role of metabolic dysfunction in degenerative diseases.

## Key facts

- **NIH application ID:** 10164492
- **Project number:** 3R01NS112672-02S1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Giovanni Manfredi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $69,480
- **Award type:** 3
- **Project period:** 2020-07-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10164492

## Citation

> US National Institutes of Health, RePORTER application 10164492, The role of the mitochondrial protein dimer CHCHD2/10 in health and disease (3R01NS112672-02S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10164492. Licensed CC0.

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