​​​​​​Talk from Michel Thiebaut de Schotten, Groupe d'Imagerie Neurofonctionnelle (CNRS, CEA, University of Bordeaux)​​​

Short abstract:​​

The human brain is one of the most energy-demanding organs, relying on mitochondrial oxidative phosphorylation (OXPHOS) to sustain its activity. In our recent study (Nature,2025), we introduced a voxelization-based approach to map mitochondrial respiratory capacity and diversity across the human brain at MRI-comparable resolution. By partitioning a coronal hemisphere into 703 voxels, we systematically profiled mitochondrial content, enzyme activities, and respiratory capacity, revealing distinct mitotypes across grey and white matter, cortical and subcortical regions, and along evolutionary gradients. These data were integrated with multimodal MRI, yielding predictive models that extend mitochondrial mapping to the whole brain, providing the first Mito Brain Map as a resource linking subcellular bioenergetics with systems-level neuroscience.
 
In this presentation, I will not only highlight the main findings of this work but also present new, unpublished results exploring inter-individual variability in mitochondrial brain organization. Specifically, I will show the first mitochondrial phenotyping data in individuals carrying single mtDNA deletions and the common pathogenic variant m.3243A>G and MELAS. These findings reveal how inherited mitochondrial defects reshape the energetical architecture of the human brain, offering novel insights into the vulnerability of specific neural systems in mitochondrial disease.