Mitochondria are often described as the powerhouses of the cell, but their role in the brain may be even more important than scientists once realized. These tiny structures provide the energy neurons need to communicate, form memories, and keep the brain working smoothly.
In a study published in Nature Neuroscience, researchers from Inserm and the NeuroCentre Magendie at the University of Bordeaux, in collaboration with scientists from the University of Moncton in Canada, reported a major step forward in our understanding of dementia. Their results showed a direct causal relationship between defects in mitochondrial activity and cognitive symptoms associated with neurodegenerative diseases.
brain energy and memory loss
The research team has created a highly specific tool that can temporarily increase mitochondrial activity in animal models of neurodegenerative diseases. When they strengthened the brain’s energy mechanisms, memory problems improved.
Although this finding is still in its infancy and was observed in an animal model, it raises the intriguing possibility that mitochondria may not simply be destroyed after a brain disease begins. Rather, their failures may promote the symptoms that develop as dementia progresses.
The idea could change the way scientists think about future treatments. If energy failure in brain cells contributes to memory loss, restoring mitochondrial function may one day be a strategy to delay or alleviate symptoms.
Why are mitochondria important in the brain?
Mitochondria are small structures within cells that help produce the energy needed for normal function. This is especially important in the brain, which consumes a large amount of the body’s energy.
Neurons depend on their energy to send signals to each other. When mitochondrial activity decreases, neurons may lose enough power to function normally. Over time, that lack of energy can weaken communication in the brain and cause problems with memory and thinking.
Neurodegenerative diseases result in a gradual decline in nerve function and subsequent death of brain cells. Researchers have long observed that in Alzheimer’s disease, mitochondrial problems appear along with neuron degeneration, often before the cells die. However, until recently, it has been difficult to determine whether mitochondrial dysfunction contributed to disease progression or was simply a consequence of it.
Tools designed to recharge mitochondria
To explore this question, researchers developed a tool that can temporarily stimulate mitochondrial activity. Their reasoning was simple but powerful. If increased mitochondrial activity improves the animal’s symptoms, it would suggest that mitochondrial damage precedes neuronal loss and may directly contribute to cognitive decline.
Previous work by the research team had already identified the role of G proteins, which have a specific role in regulating mitochondrial activity in the brain to enable information transmission within cells. In a 2025 study, researchers constructed an artificial receptor called mitoDreadd-Gs. This receptor is designed to directly activate G proteins within the mitochondria, thereby stimulating mitochondrial activity.
When mitoDreadd-Gs was activated in the brain, mitochondrial activity returned to normal levels. Memory performance was also improved in a mouse model of dementia.
Potential new targets for dementia research
“This study is the first to establish a causal link between mitochondrial dysfunction and symptoms associated with neurodegenerative diseases, suggesting that reduced mitochondrial activity may be responsible for the development of neurodegeneration,” explains Giovanni Marsicano, Inserm’s principal investigator and co-senior author of the study.
Results do not mean the patient is ready for treatment. Although this study was conducted in an animal model, more research is needed to determine whether a similar approach is safe, durable, and effective in humans.
Still, the findings provide momentum for changes in dementia research. Scientists are now looking beyond the well-known hallmarks of Alzheimer’s disease, such as amyloid plaques and tau tangles, to examine how energy production, metabolism, inflammation, and cellular stress shape Alzheimer’s disease from its earliest stages.
Recent research continues to strengthen that broader perspective. A recent Mayo Clinic study links disruption of mitochondrial complex I, a critical part of the cell’s energy system, to Alzheimer’s disease progression and potential treatment response. A subsequently published review described mitochondrial dysfunction as an early and potentially central feature of Alzheimer’s disease biology, rather than simply a late consequence of brain injury.
“While these results need to be expanded upon, they provide a deeper understanding of the critical role of mitochondria in the proper functioning of the brain. Ultimately, the tools we have developed may help identify the molecular and cellular mechanisms underlying dementia and facilitate the development of effective therapeutic targets,” explains Etienne Hebert-Chatrand, a professor at the University of Moncton and co-senior author of the study.
what happens next
The next big question is whether long-term stimulation of mitochondrial activity does more than improve memory symptoms. Researchers now want to know whether restoring mitochondrial function can slow neuron loss, slow disease progression, or prevent damage before it becomes irreversible.
“Our study is now attempting to measure the effects of continuous stimulation of mitochondrial activity to see if it can influence the symptoms of neurodegenerative diseases and ultimately slow or even prevent neuronal cell loss if mitochondrial activity is restored,” added Luigi Bellocchio, a researcher at Inserm and co-senior author of the study.
So far, the findings offer a striking message. Memory loss may involve not only dying brain cells, but also living neurons that are starved of energy. By learning how to recharge these tiny engines, scientists may open up new avenues in the fight against dementia.
