PMID- 38496679
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240325
DP  - 2024 Mar 7
TI  - A Human Brain Map of Mitochondrial Respiratory Capacity and Diversity.
LID - 2024.03.05.583623 [pii]
LID - 10.1101/2024.03.05.583623 [doi]
AB  - 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 (3x3x3 
      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.
FAU - Mosharov, Eugene V
AU  - Mosharov EV
AD  - Department of Psychiatry, Divisions of Molecular Therapeutics and Behavioral 
      Medicine, Columbia University Irving Medical Center, New York, NY, USA.
AD  - New York State Psychiatric Institute, New York, NY, USA.
FAU - Rosenberg, Ayelet M
AU  - Rosenberg AM
AD  - Department of Psychiatry, Divisions of Molecular Therapeutics and Behavioral 
      Medicine, Columbia University Irving Medical Center, New York, NY, USA.
FAU - Monzel, Anna S
AU  - Monzel AS
AD  - Department of Psychiatry, Divisions of Molecular Therapeutics and Behavioral 
      Medicine, Columbia University Irving Medical Center, New York, NY, USA.
FAU - Osto, Corey A
AU  - Osto CA
AD  - Department of Medicine, Endocrinology, and Department of Molecular and Medical 
      Pharmacology, David Geffen School of Medicine, University of California, Los 
      Angeles, CA.
FAU - Stiles, Linsey
AU  - Stiles L
AD  - Department of Medicine, Endocrinology, and Department of Molecular and Medical 
      Pharmacology, David Geffen School of Medicine, University of California, Los 
      Angeles, CA.
FAU - Rosoklija, Gorazd B
AU  - Rosoklija GB
AD  - New York State Psychiatric Institute, New York, NY, USA.
AD  - Department of Psychiatry, Division of Molecular Imaging and Neuropathology, 
      Columbia University Irving Medical Center, New York, NY, USA.
FAU - Dwork, Andrew J
AU  - Dwork AJ
AD  - New York State Psychiatric Institute, New York, NY, USA.
AD  - Department of Psychiatry, Division of Molecular Imaging and Neuropathology, 
      Columbia University Irving Medical Center, New York, NY, USA.
AD  - Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
FAU - Bindra, Snehal
AU  - Bindra S
AUID- ORCID: 0000-0002-8865-4249
AD  - Department of Psychiatry, Divisions of Molecular Therapeutics and Behavioral 
      Medicine, Columbia University Irving Medical Center, New York, NY, USA.
FAU - Zhang, Ya
AU  - Zhang Y
AD  - 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.
FAU - Fujita, Masashi
AU  - Fujita M
AD  - 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.
FAU - Mariani, Madeline B
AU  - Mariani MB
AD  - New York State Psychiatric Institute, New York, NY, USA.
AD  - Department of Psychiatry, Division of Molecular Imaging and Neuropathology, 
      Columbia University Irving Medical Center, New York, NY, USA.
FAU - Bakalian, Mihran
AU  - Bakalian M
AD  - New York State Psychiatric Institute, New York, NY, USA.
AD  - Department of Psychiatry, Division of Molecular Imaging and Neuropathology, 
      Columbia University Irving Medical Center, New York, NY, USA.
FAU - Sulzer, David
AU  - Sulzer D
AD  - Department of Psychiatry, Divisions of Molecular Therapeutics and Behavioral 
      Medicine, Columbia University Irving Medical Center, New York, NY, USA.
AD  - New York State Psychiatric Institute, New York, NY, USA.
AD  - 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.
FAU - De Jager, Philip L
AU  - De Jager PL
AUID- ORCID: 0000-0002-8057-2505
AD  - 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.
FAU - Menon, Vilas
AU  - Menon V
AD  - 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.
FAU - Shirihai, Orian S
AU  - Shirihai OS
AD  - Department of Medicine, Endocrinology, and Department of Molecular and Medical 
      Pharmacology, David Geffen School of Medicine, University of California, Los 
      Angeles, CA.
FAU - Mann, J John
AU  - Mann JJ
AD  - New York State Psychiatric Institute, New York, NY, USA.
AD  - Department of Psychiatry, Division of Molecular Imaging and Neuropathology, 
      Columbia University Irving Medical Center, New York, NY, USA.
FAU - Underwood, Mark
AU  - Underwood M
AD  - New York State Psychiatric Institute, New York, NY, USA.
AD  - Department of Psychiatry, Division of Molecular Imaging and Neuropathology, 
      Columbia University Irving Medical Center, New York, NY, USA.
FAU - Boldrini, Maura
AU  - Boldrini M
AD  - New York State Psychiatric Institute, New York, NY, USA.
AD  - Department of Psychiatry, Division of Molecular Imaging and Neuropathology, 
      Columbia University Irving Medical Center, New York, NY, USA.
FAU - de Schotten, Michel Thiebaut
AU  - de Schotten MT
AUID- ORCID: 0000-0002-0329-1814
AD  - Brain Connectivity and Behavior Laboratory, Paris, France; Groupe d'Imagerie 
      Neurofonctionnelle, Institut des Maladies Neurodegeneratives-UMR 5293, CNRS, CEA 
      University of Bordeaux, France.
FAU - Picard, Martin
AU  - Picard M
AD  - Department of Psychiatry, Divisions of Molecular Therapeutics and Behavioral 
      Medicine, Columbia University Irving Medical Center, New York, NY, USA.
AD  - New York State Psychiatric Institute, New York, NY, USA.
AD  - Department of Neurology, H. Houston Merritt Center, Columbia Translational 
      Neuroscience Initiative, Columbia University Irving Medical Center, New York, NY, 
      USA.
AD  - Robert N Butler Columbia Aging Center, Columbia University Mailman School of 
      Public Health, New York, NY, USA.
LA  - eng
GR  - RF1 AG057473/AG/NIA NIH HHS/United States
GR  - RF1 AG076821/AG/NIA NIH HHS/United States
PT  - Preprint
DEP - 20240307
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
PMC - PMC10942385
OTO - NOTNLM
OT  - MRI
OT  - OxPhos
OT  - anatomical mapping
OT  - brain voxelization
OT  - mitochondria
OT  - neuroimaging
OT  - phenotyping
OT  - single-cell RNA sequencing
COIS- Financial competing interests The authors have no competing interests to declare.
EDAT- 2024/03/18 06:44
MHDA- 2024/03/18 06:45
PMCR- 2024/03/15
CRDT- 2024/03/18 04:40
PHST- 2024/03/18 06:44 [pubmed]
PHST- 2024/03/18 06:45 [medline]
PHST- 2024/03/18 04:40 [entrez]
PHST- 2024/03/15 00:00 [pmc-release]
AID - 2024.03.05.583623 [pii]
AID - 10.1101/2024.03.05.583623 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2024 Mar 7:2024.03.05.583623. doi: 10.1101/2024.03.05.583623.