Impaired recycling of mitochondria in autism?

Impaired recycling of mitochondria in autism?
These iPSC-derived cortical neurons from a patient with tuberous sclerosis complex show a large number of dysfunctional mitochondria (red/green). The cell nuclei are stained blue. Credit: Sahin Lab


Mitochondria, the organelles responsible for cellular energy production and metabolism, constantly get recycled. Through a process known as autophagy ("self-eating"), cells literally digest their damaged or aging mitochondria, clearing the way for healthy replacements. (Research on how autophagy works earned a Nobel Prize earlier this month.)

The new study, led by Mustafa Sahin, MD, PhD, and co-first authors Darius Ebrahimi-Fakhari, MD, PhD, a resident at Boston Children's Hospital, and medical student Afshin Saffari, in Boston Children's F.M. Kirby Neurobiology Center, shows that autophagy is defective in TSC. The scientists further showed that two existing classes of drugs counter the defect: the epilepsy drug carbamazepine, and drugs known as mTOR inhibitors. When treated, the dysfunctional neurons were able to clear damaged mitochondria and replenish healthy mitochondria, restoring a normal turnover.

"Our findings point to possible treatments for enhancing mitophagy for some neurodevelopmental and neurodegenerative diseases," says Sahin, who is also director of the Translational Neuroscience Center at Boston Children's and senior author on the paper.

Out with the old, in with the new

Defects in mitophagy, or autophagy of mitochondria, have already been implicated in a number of such as Parkinson's disease and Alzheimer's disease. Mitochondria have also been studied in autism for years, but the findings have been largely anecdotal and inconclusive, in part because the autism population is diverse and hard to define.

"We decided to use , a genetically defined disorder that has a high incidence of autism, as a model to understand the role of mitochondrial dynamics," says Sahin.


Axons take the hit


"We think this could have implications for how neurons talk to each other," says Ebrahimi-Fakhari. "Synapses that lose the support of mitochondria might be releasing neurotransmitters too much or too little."


Therapeutic opportunity?


  • by reintroducing a healthy copy of the gene mutated in TSC

Most notably, were replenished at presynaptic sites, where their presence is most critical.


"Our work defines mitochondrial homeostasis as a therapeutic target for TSC, and may also have implications for other neurological diseases that involve mitochondrial dysfunction," says Ebrahimi-Fakhari.

Explore further

Mobilizing mitochondria may be key to regenerating damaged neurons

Journal information: Cell Reports

Citation: Impaired recycling of mitochondria in autism? (2016, October 18) retrieved 14 June 2021 from https://medicalxpress.com/news/2016-10-impaired-recycling-mitochondria-autism.html

Feedback to editors

User comments