How mitochondrial problems and autism-linked genes change neurons
Resolving the relationship between mitochondrial dysfunction and the impact of non-syndromic autism spectrum disorder-related risk genes on neuronal structure and function
This project tests whether mild mitochondrial problems make certain autism-related gene changes more likely to harm how brain cells form and connect in people with non-syndromic autism.
Quick facts
| Grant type | R21 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Icahn School of Medicine at Mount Sinai NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project ID | NIH-11319789 on NIH RePORTER |
What this research studies
Researchers are using patient-derived stem cells turned into neurons to model a "two-hit" combination of autism-linked gene changes and mild mitochondrial dysfunction. They will create cell lines carrying mutations in PPP2R5D, SHANK3, or GRIN2B together with about 30% mitochondrial DNA heteroplasmy to mimic reduced neuronal bioenergetics. Using both 2D neurons and 3D brain organoids, the team will image and reconstruct neurons and networks, measure soma size and dendritic morphology, and count synapses. The goal is to link these combined genetic and mitochondrial changes to how neurons develop and form connections, which could point to new targets to help people with non-syndromic autism.
Who could benefit from this research
Good fit: People with non-syndromic autism who carry changes in PPP2R5D, SHANK3, or GRIN2B or who have known mitochondrial DNA heteroplasmy would be most relevant for this research.
Not a fit: Individuals without these specific gene changes or mitochondrial DNA differences, or those with syndromic forms of autism unrelated to these genes, are less likely to benefit directly from these findings.
Why it matters
Potential benefit: If successful, this work could explain variability in autism symptoms and suggest mitochondrial-focused strategies to improve brain development or function.
How similar studies have performed: iPSC-derived neurons and brain organoids have been used successfully before to model autism and mitochondrial defects, but pairing specific autism genes with controlled mtDNA heteroplasmy is a novel approach.
Where this research is happening
New York, United States
- Icahn School of Medicine at Mount Sinai — New York, United States (Active)
Researchers
- Principal investigator: Kozicz, Laszlo Tamas — Icahn School of Medicine at Mount Sinai
- Study coordinator: Kozicz, Laszlo Tamas
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.