An energy blueprint of the human brain

Abstract

Functional neuroimaging enables measurement of brain organization and dynamics, but it only indirectly measures the subcellular bioenergetic processes that power brain activity. As such, there has been a gap between these large-scale imaging techniques and the microscopic scale of mitochondrial bioenergetics. In their study published in Nature, Mosharov and colleagues present a method to bridge this gap by creating a spatial map of mitochondrial diversity across the brain. They cut frozen human brain tissue into 3-mm cubes, comparable in size to MRI voxels, and then registered them to MNI space. They used advanced biochemical assays to profile mitochondrial distribution and function, which were then compared with standard brain-imaging data from different modalities. The findings revealed substantial heterogeneity in mitochondrial density and oxidative phosphorylation capacity between gray and white matter. The distribution of mitochondria is suggestive of a gradient that aligns with the phylogenetic development of the brain. This study offers insight into the energetic infrastructure that supports brain function, and it has the potential to inform research into healthy brain development and disease.

Original reference: Nature https://doi.org/10.1038/s41586-025-08740-6 (2025)