Scientists have revealed the assembly of the first brain mitochondria map, which they say could mark a significant first step toward unraveling age-related brain disorders.
Mitochondria generate the energy powering brain cells, making them essential for cognitive function. However, the new MitoBrainMap shows that evolutionarily older areas of the brain contain lower mitochondria densities.
The brain uses an enormous amount of the body’s energy—about 20%—most of which comes from mitochondrial oxidative phosphorylation. This new research bridges a crucial gap in cognitive neuroscience by helping explain how cellular-level activity affects cognitive performance. The researchers hope to shed new light on cognitive decline by mapping the brain’s molecular energetic landscape.
For context, German neuroscientist Valentin Riedl, who was not involved in the project, commented that it is “both technically impressive and conceptually groundbreaking.”
“The biology of the brain, we know now, is deeply intertwined with the energetics of the brain,” said co-author Martin Picard, a psychobiologist at Columbia University in New York City.
Slicing into the Problem
Researchers conducted their work using the donated brain of a 54-year-old heart attack victim. They sliced the frozen brain into 703 cubes, each 3 millimeters per side. The chosen size roughly matched the resolution of a standard 3D brain scan, but handling such a high number of samples proved challenging. Using molecular and biochemical techniques, the team identified mitochondrial density in each sample and estimated energy production efficiency in a subset of them.
Following the lab work, the researchers developed a computer model to predict the type and density of mitochondria throughout the brain. They trained the model using a portion of their collected data, then successfully applied it to additional brain slices with accurate results.
Evolutionary Energy
The study revealed how mitochondrial distribution and energy production vary across different brain regions. Gray matter contains about 1.5 times more mitochondria than white matter. While white matter features long neuron branches for transmitting signals, gray matter houses the compact central structures of neurons. Despite containing fewer mitochondria overall, gray matter mitochondria generate energy more efficiently. The brain’s wrinkled gray cortex—one of the most recent evolutionary developments from reptiles to primates—proved to be the most energy-efficient region.
Researchers continue to gather evidence linking psychiatric and age-related brain diseases to mitochondrial changes. The MitoBrainMap will be essential for studying and tracking those changes. Further research is needed to expand understanding of how mitochondria differ across brain regions and individuals.
The team has already launched a follow-up project mapping nine regions in 500 human brains. With this larger sample size, they say future studies will allow for critical comparisons between healthy individuals and those affected by neurological, psychiatric, and neurodegenerative disorders.
The paper “A Human Brain Map of Mitochondrial Respiratory Capacity and Diversity” appeared on March 24, 2025, in Nature.
Ryan Whalen covers science and technology for The Debrief. He holds an MA in History and a Master of Library and Information Science with a certificate in Data Science. He can be contacted at ryan@thedebrief.org, and follow him on Twitter @mdntwvlf.