{"id":182198,"date":"2025-03-27T10:48:16","date_gmt":"2025-03-27T09:48:16","guid":{"rendered":"https:\/\/www.bordeaux-neurocampus.fr\/?p=182198"},"modified":"2025-03-27T11:53:15","modified_gmt":"2025-03-27T10:53:15","slug":"a-human-brain-map-of-mitochondrial-respiratory-capacity-and-diversity","status":"publish","type":"post","link":"https:\/\/www.bordeaux-neurocampus.fr\/en\/a-human-brain-map-of-mitochondrial-respiratory-capacity-and-diversity\/","title":{"rendered":"A human brain map of mitochondrial respiratory capacity and diversity"},"content":{"rendered":"<p><a href=\"https:\/\/www.cnrs.fr\/fr\/presse\/premiere-cartographie-des-centrales-energetiques-du-cerveau-humain-0\">Michel Thiebaut de Schotten<\/a> (CNRS, IMN),<span class=\"break-words tvm-parent-container\"><span dir=\"ltr\"> Eugene V. Mosharov et Martin Picard (Columbia University Irving Medical Center<em>) <\/em>have developed an innovative approach to bridge cellular biology and cognitive neuroscience by mapping mitochondrial function across the human brain at neuroimaging resolution.<\/span><\/span><\/p>\n<div class=\"introduction\">\n<div class=\"clearfix text-formatted field field--name-field-press-info-header field--type-text-long field--label-hidden field__item\">\n<div class=\"tex2jax_process\">\n<h3>Abstract<\/h3>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright wp-image-182203\" src=\"https:\/\/www.bordeaux-neurocampus.fr\/wp-content\/uploads\/2025\/03\/deschotten-nature-2025-2-360x296.jpg\" alt=\"\" width=\"263\" height=\"216\" srcset=\"https:\/\/www.bordeaux-neurocampus.fr\/wp-content\/uploads\/2025\/03\/deschotten-nature-2025-2-360x296.jpg 360w, https:\/\/www.bordeaux-neurocampus.fr\/wp-content\/uploads\/2025\/03\/deschotten-nature-2025-2-768x631.jpg 768w, https:\/\/www.bordeaux-neurocampus.fr\/wp-content\/uploads\/2025\/03\/deschotten-nature-2025-2.jpg 770w\" sizes=\"auto, (max-width: 263px) 100vw, 263px\" \/>Mitochondrial oxidative phosphorylation (OXPHOS)\u00a0powers brain activity<sup><a id=\"ref-link-section-d106344660e762\" title=\"Shulman, R. G., Hyder, F. &amp; Rothman, D. L. Baseline brain energy supports the state of consciousness. Proc. Natl Acad. Sci. USA 106, 11096\u201311101 (2009).\" href=\"https:\/\/www.nature.com\/articles\/s41586-025-08740-6#ref-CR1\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 1\">1<\/a>,<a id=\"ref-link-section-d106344660e765\" title=\"Zhang, D. &amp; Raichle, M. E. Disease and the brain\u2019s dark energy. Nat. Rev. Neurol. 6, 15\u201328 (2010).\" href=\"https:\/\/www.nature.com\/articles\/s41586-025-08740-6#ref-CR2\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 2\">2<\/a><\/sup>, and mitochondrial defects are linked to neurodegenerative and neuropsychiatric disorders<sup><a id=\"ref-link-section-d106344660e769\" title=\"Minhas, P. S. et al. Restoring metabolism of myeloid cells reverses cognitive decline in ageing. Nature 590, 122\u2013128 (2021).\" href=\"https:\/\/www.nature.com\/articles\/s41586-025-08740-6#ref-CR3\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 3\">3<\/a>,<a id=\"ref-link-section-d106344660e772\" title=\"Daniels, T. E., Olsen, E. M. &amp; Tyrka, A. R. Stress and psychiatric disorders: the role of mitochondria. Annu. Rev. Clin. Psychol. 16, 165\u2013186 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41586-025-08740-6#ref-CR4\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 4\">4<\/a><\/sup>. To understand the basis of brain activity and behaviour, there is a need to define the molecular energetic landscape of the brain<sup><a id=\"ref-link-section-d106344660e776\" title=\"Rosenberg, A. M. et al. Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice. Nat. Commun. 14, 4726 (2023).\" href=\"https:\/\/www.nature.com\/articles\/s41586-025-08740-6#ref-CR5\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\">5<\/a>,<a id=\"ref-link-section-d106344660e776_1\" title=\"Fecher, C. et al. Cell-type-specific profiling of brain mitochondria reveals functional and molecular diversity. Nat. Neurosci. 22, 1731\u20131742 (2019).\" href=\"https:\/\/www.nature.com\/articles\/s41586-025-08740-6#ref-CR6\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\">6<\/a>,<a id=\"ref-link-section-d106344660e776_2\" title=\"Tomasi, D., Wang, G.-J. &amp; Volkow, N. D. Energetic cost of brain functional connectivity. Proc. Natl Acad. Sci. USA 110, 13642\u201313647 (2013).\" href=\"https:\/\/www.nature.com\/articles\/s41586-025-08740-6#ref-CR7\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\">7<\/a>,<a id=\"ref-link-section-d106344660e776_3\" title=\"He, X. et al. Uncovering the biological basis of control energy: structural and metabolic correlates of energy inefficiency in temporal lobe epilepsy. Sci. Adv. 8, eabn2293 (2022).\" href=\"https:\/\/www.nature.com\/articles\/s41586-025-08740-6#ref-CR8\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\">8<\/a>,<a id=\"ref-link-section-d106344660e776_4\" title=\"Yu, Y. et al. A 3D atlas of functional human brain energetic connectome based on neuropil distribution. Cereb. Cortex 33, 3996\u20134012 (2023).\" href=\"https:\/\/www.nature.com\/articles\/s41586-025-08740-6#ref-CR9\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\">9<\/a>,<a id=\"ref-link-section-d106344660e779\" title=\"Blazey, T. et al. Quantitative positron emission tomography reveals regional differences in aerobic glycolysis within the human brain. J. Cereb. Blood Flow Metab. 39, 2096\u20132102 (2019).\" href=\"https:\/\/www.nature.com\/articles\/s41586-025-08740-6#ref-CR10\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 10\">10<\/a><\/sup>. Here, to bridge the scale gap between cognitive neuroscience and cell biology, we developed a physical voxelization approach to partition a frozen human coronal hemisphere section into 703 voxels comparable to neuroimaging resolution (3\u2009\u00d7\u20093\u2009\u00d7\u20093\u2009mm). In each cortical and subcortical brain voxel, we profiled mitochondrial phenotypes, including OXPHOS enzyme\u00a0activities, mitochondrial DNA and volume density, and mitochondria-specific respiratory capacity. We show that the human brain contains diverse mitochondrial phenotypes driven by both topology and cell types. Compared with white matter, grey matter contains &gt;50% more mitochondria. Moreover, the mitochondria in grey matter are biochemically optimized for energy transformation, particularly among recently evolved cortical brain regions. Scaling these data to the whole brain, we created a backwards linear regression model that integrates several neuroimaging modalities<sup><a id=\"ref-link-section-d106344660e783\" title=\"Tsuchida, A. et al. The MRi-Share database: brain imaging in a cross-sectional cohort of 1870 university students. Brain Struct. Funct. 226, 2057\u20132085 (2021).\" href=\"https:\/\/www.nature.com\/articles\/s41586-025-08740-6#ref-CR11\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 11\">11<\/a><\/sup> to generate a brain-wide map of mitochondrial distribution and specialization. This model predicted mitochondrial characteristics in an independent brain region of the same donor brain. This approach and the resulting MitoBrainMap of mitochondrial phenotypes provide a foundation for exploring the molecular energetic landscape that enables normal brain function. This resource also relates to neuroimaging data and defines the subcellular basis for regionalized brain processes relevant to neuropsychiatric and neurodegenerative disorders. All data are available at <a href=\"http:\/\/humanmitobrainmap.bcblab.com\">http:\/\/humanmitobrainmap.bcblab.com<\/a>.<\/p>\n<hr \/>\n<h3 class=\"field__label\">Reference<\/h3>\n<div class=\"field__item\">\n<div class=\"tex2jax_process\">\n<p><strong>A Human Brain Map of Mitochondrial Respiratory Capacity and Diversity.<\/strong> Eugene V. Mosharov, Ayelet M. Rosenberg, Anna S. Monzel, Corey A. Osto, Linsey Stiles, Gorazd B. Rosoklija, Andrew J. Dwork, Snehal Bindra, Alex Junker, Ya Zhang, Masashi Fujita, Madeline B. Mariani, Mihran Bakalian, David Sulzer, Philip L. De Jager, Vilas Menon, Orian S. Shirihai, J. John Mann, Mark Underwood, Maura Boldrini, Michel Thiebaut de Schotten* et Martin Picard*. <em>Nature<\/em>, le 26 mars 2025.<br \/>\n<strong>DOI <\/strong>: <a class=\"ext\" href=\"https:\/\/doi.org\/10.1038\/s41586-025-08740-6\" target=\"_blank\" rel=\"noreferrer noopener\" data-extlink=\"\">https:\/\/doi.org\/10.1038\/s41586-025-08740-6<\/a><\/p>\n<h3><strong>Summary:\u00a0<\/strong>A map of mitochondrial biology reveals the energy landscape of the human brain<\/h3>\n<p><a href=\"https:\/\/www.nature.com\/articles\/d41586-025-00872-z\">https:\/\/www.nature.com\/articles\/d41586-025-00872-z<\/a><\/p>\n<hr \/>\n<h3>About it (in french)<\/h3>\n<p><strong>CNRS Le Journal : \u00a0<\/strong><a class=\"ext\" href=\"https:\/\/lejournal.cnrs.fr\/articles\/carte-energie-cerveau-mitochondries-decouverte\" target=\"_blank\" rel=\"noreferrer noopener\" data-extlink=\"\">https:\/\/lejournal.cnrs.fr\/articles\/carte-energie-cerveau-mitochondries-decouverte<\/a><\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Michle Thiebaut de Schotten in Nature<\/p>\n","protected":false},"author":108,"featured_media":182200,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[71,1],"tags":[],"class_list":["post-182198","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-highlight-en","category-news-neurocampus"],"_links":{"self":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts\/182198","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/users\/108"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/comments?post=182198"}],"version-history":[{"count":2,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts\/182198\/revisions"}],"predecessor-version":[{"id":182236,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts\/182198\/revisions\/182236"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/media\/182200"}],"wp:attachment":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/media?parent=182198"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/categories?post=182198"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/tags?post=182198"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}