A Human Brain Map of Mitochondrial Respiratory Capacity and Diversity.

Autor:	Mosharov EV; Department of Psychiatry, Divisions of Molecular Therapeutics and Behavioral Medicine, Columbia University Irving Medical Center, New York, NY, USA.; New York State Psychiatric Institute, New York, NY, USA., Rosenberg AM; Department of Psychiatry, Divisions of Molecular Therapeutics and Behavioral Medicine, Columbia University Irving Medical Center, New York, NY, USA., Monzel AS; Department of Psychiatry, Divisions of Molecular Therapeutics and Behavioral Medicine, Columbia University Irving Medical Center, New York, NY, USA., Osto CA; Department of Medicine, Endocrinology, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA., Stiles L; Department of Medicine, Endocrinology, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA., Rosoklija GB; New York State Psychiatric Institute, New York, NY, USA.; Department of Psychiatry, Division of Molecular Imaging and Neuropathology, Columbia University Irving Medical Center, New York, NY, USA., Dwork AJ; New York State Psychiatric Institute, New York, NY, USA.; Department of Psychiatry, Division of Molecular Imaging and Neuropathology, Columbia University Irving Medical Center, New York, NY, USA.; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA., Bindra S; Department of Psychiatry, Divisions of Molecular Therapeutics and Behavioral Medicine, Columbia University Irving Medical Center, New York, NY, USA., Zhang Y; Center for Translational & Computational Neuroimmunology, Neuroimmunology Division, Department of Neurology and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA., Fujita M; Center for Translational & Computational Neuroimmunology, Neuroimmunology Division, Department of Neurology and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA., Mariani MB; New York State Psychiatric Institute, New York, NY, USA.; Department of Psychiatry, Division of Molecular Imaging and Neuropathology, Columbia University Irving Medical Center, New York, NY, USA., Bakalian M; New York State Psychiatric Institute, New York, NY, USA.; Department of Psychiatry, Division of Molecular Imaging and Neuropathology, Columbia University Irving Medical Center, New York, NY, USA., Sulzer D; Department of Psychiatry, Divisions of Molecular Therapeutics and Behavioral Medicine, Columbia University Irving Medical Center, New York, NY, USA.; New York State Psychiatric Institute, New York, NY, USA.; Departments of Neurology and Pharmacology, Columbia University Irving Medical Center, New York, NY, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA., De Jager PL; Center for Translational & Computational Neuroimmunology, Neuroimmunology Division, Department of Neurology and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA., Menon V; Center for Translational & Computational Neuroimmunology, Neuroimmunology Division, Department of Neurology and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA., Shirihai OS; Department of Medicine, Endocrinology, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA., Mann JJ; New York State Psychiatric Institute, New York, NY, USA.; Department of Psychiatry, Division of Molecular Imaging and Neuropathology, Columbia University Irving Medical Center, New York, NY, USA., Underwood M; New York State Psychiatric Institute, New York, NY, USA.; Department of Psychiatry, Division of Molecular Imaging and Neuropathology, Columbia University Irving Medical Center, New York, NY, USA., Boldrini M; New York State Psychiatric Institute, New York, NY, USA.; Department of Psychiatry, Division of Molecular Imaging and Neuropathology, Columbia University Irving Medical Center, New York, NY, USA., Thiebaut de Schotten M; Brain Connectivity and Behavior Laboratory, Paris, France; Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives-UMR 5293, CNRS, CEA University of Bordeaux, France., Picard M; Department of Psychiatry, Divisions of Molecular Therapeutics and Behavioral Medicine, Columbia University Irving Medical Center, New York, NY, USA.; New York State Psychiatric Institute, New York, NY, USA.; Department of Neurology, H. Houston Merritt Center, Columbia Translational Neuroscience Initiative, Columbia University Irving Medical Center, New York, NY, USA.; Robert N Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York, NY, USA.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2024 Mar 22. Date of Electronic Publication: 2024 Mar 22.
DOI:	10.21203/rs.3.rs-4047706/v1
Abstrakt:	Mitochondrial oxidative phosphorylation (OxPhos) powers brain activity ^1,2 , and mitochondrial defects are linked to neurodegenerative and neuropsychiatric disorders ^3,4 , underscoring the need to define the brain's molecular energetic landscape ^5-10 . To bridge the cognitive neuroscience and cell biology scale gap, we developed a physical voxelization approach to partition a frozen human coronal hemisphere section into 703 voxels comparable to neuroimaging resolution (3×3×3 mm). In each cortical and subcortical brain voxel, we profiled mitochondrial phenotypes including OxPhos enzyme activities, mitochondrial DNA and volume density, and mitochondria-specific respiratory capacity. We show that the human brain contains a diversity of mitochondrial phenotypes driven by both topology and cell types. Compared to white matter, grey matter contains >50% more mitochondria. We show that the more abundant grey matter mitochondria also are biochemically optimized for energy transformation, particularly among recently evolved cortical brain regions. Scaling these data to the whole brain, we created a backward linear regression model integrating several neuroimaging modalities ¹¹ , thereby generating a brain-wide map of mitochondrial distribution and specialization that predicts mitochondrial characteristics in an independent brain region of the same donor brain. This new approach and the resulting MitoBrainMap of mitochondrial phenotypes provide a foundation for exploring the molecular energetic landscape that enables normal brain functions, relating it to neuroimaging data, and defining the subcellular basis for regionalized brain processes relevant to neuropsychiatric and neurodegenerative disorders. Competing Interests: Financial competing interests The authors have no competing interests to declare.
Databáze:	MEDLINE
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