Evidence map›Paper›PMID 38979162›Full record

ArticlebioRxiv : the preprint server for biology2024

MICOS Complex Loss Governs Age-Associated Murine Mitochondrial Architecture and Metabolism in the Liver, While Sam50 Dictates Diet Changes.

Zer Vue, Alexandria Murphy, Han Le, Kit Neikirk, Edgar Garza-Lopez, Andrea G Marshall, Margaret Mungai, Brenita Jenkins, Larry Vang, Heather K Beasley and 47 more

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In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

57 authors.

Zer VueDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Alexandria MurphyDepartment of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, State College, PA 16801.
Han LeDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Kit NeikirkDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Edgar Garza-LopezDepartment of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA.
Andrea G MarshallDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Margaret MungaiDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Brenita JenkinsDepartment of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, State College, PA 16801.
Larry VangDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Heather K BeasleyDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Mariaassumpta EzedimmaDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Sasha ManusDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Aaron WhitesideDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Maria Fernanda ForniDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520.
Chanel HarrisDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Amber CrabtreeDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Claude F AlbrittonDepartment of Biomedical Sciences, School of Graduate Studies, Meharry Medical College, Nashville, TN 37208-3501, USA.
Sydney JamisonDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Mert DemirciDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Praveena PrasadDepartment of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, State College, PA 16801.
Ashton OliverDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Ky'Era V ActkinsDivision of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States.
Jianqiang ShaoCentral Microscopy Research Facility, University of Iowa, Iowa City, IA, 52242, USA.
Elma ZaganjorDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Estevão ScudeseDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Benjamin RodriguezDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Alice KohDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Izabella RabagoDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Johnathan E MooreDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Desiree NguyenDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Muhammad AftabDepartment of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA.
Benjamin KirkDepartment of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA.
Yahang LiDepartment of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA.
Nelson WandiraDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Taseer AhmadDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Mohammad SaleemDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Ashlesha KadamDepartment of Internal Medicine, Section of Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157 USA.
Prasanna KattiNational Heart, Lung and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Ho-Jin KohDepartment of Biological Sciences, Tennessee State University, Nashville, TN 37209, USA.
Chantell EvansDepartment of Cell Biology, Duke University School of Medicine, Durham, NC, 27708, USA.
Young Do KooDepartment of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA.
Eric WangDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, CA, 92697, USA.
Quinton SmithDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, CA, 92697, USA.
Dhanendra TomarDepartment of Pharmacology, College of Pharmacy, University of Sargodha, Sargodha, Punjab,40100, Pakistan.ORCID 0000-0002-3144-7257
Clintoria R WilliamsDepartment of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, OH 45435 USA.
Mariya T SweetwyneDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195, USA.
Anita M QuintanaDepartment of Biological Sciences, Border Biomedical Research Center, The University of Texas at El Paso, El Paso, Texas, USA.ORCID 0000-0002-3596-1587
Mark A PhillipsDepartment of Integrative Biology, Oregon State University, Corvallis, OR, 97331, USA.ORCID 0000-0002-2319-7913
David HubertDepartment of Integrative Biology, Oregon State University, Corvallis, OR, 97331, USA.
Annet KiraboDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Chandravanu DashDepartment of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, TN, United States.ORCID 0000-0003-4466-8355
Pooja JadiyaDepartment of Internal Medicine, Section of Gerontology and Geriatric Medicine, Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest University School of Medicine, Winston-Salem, NC.
André KinderArtur Sá Earp Neto University Center - UNIFASE-FMP, Petrópolis Medical School, Brazil.
Olujimi A AjijolaUCLA Cardiac Arrhythmia Center, University of California, Los Angeles, CA, USA.
Tyne W Miller-FlemingDivision of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States.
Melanie R McReynoldsDepartment of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, State College, PA 16801.
Antentor HintonDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.ORCID 0000-0002-7730-952X

Funding

Vanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasmaUL1TR002243 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul A. Harris, Wesley H Self · 2017 to 2026
$130.7M
VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
Vanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI OWEN P MCGUINNESS · 2012 to 2026
$29.3M
Tennessee CFAR: Implementation of Culturally Responsive Trauma-Informed Care with Youth with HIV in Memphis, TNP30AI110527 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI John Koethe · 2015 to 2026
$27.5M
Wake Forest University School of Medicine Alzheimer's Disease Research CenterP30AG072947 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Sharon Letchworth · 2021 to 2026
$24.3M
Pharmacogenomics of Arrhythmia TherapyU19HL065962 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RODEN, DAN M · 2010 to 2014
$17.4M
MULTIDISCIPLINARY TRAINING IN MOLECULAR ENDOCRINOLOGYT32DK007563 · NIDDK · VANDERBILT UNIVERSITY · PI Richard M O'Brien · 1988 to 2026
$15.9M
Understanding and preventing HLA-associated drug reactionsP50GM115305 · NIGMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PHILLIPS, ELIZABETH, RODEN, DAN M · 2015 to 2019
$13.0M
The Genetic Epemiology of Multiple SclerosisR01NS032830 · NINDS · VANDERBILT UNIVERSITY · PI HAINES, JONATHAN L · 1995 to 2010
$8.9M
Epidemiologic Architecture for Genes Linked to Environment (EAGLE)U01HG004798 · NHGRI · VANDERBILT UNIVERSITY · PI CRAWFORD, DANA C · 2008 to 2013
$8.8M
VESPA: Vanderbilt Electronic Systems for Pharmacogenomic AssessmentRC2GM092618 · NIGMS · VANDERBILT UNIVERSITY · PI DENNY, JOSHUA C., RODEN, DAN M · 2009 to 2010
$6.4M
BLRD VA I01 BX005352NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1 TR002243NCRR NIH HHS S10 RR025141NCRR NIH HHS UL1 RR024975NHGRI NIH HHS U01 HG004798NHGRI NIH HHS U01 HG006378NHLBI NIH HHS R01 HL144941NHLBI NIH HHS R01 HL147818NHLBI NIH HHS R03 HL155041NHLBI NIH HHS R25 HL106365NHLBI NIH HHS U19 HL065962NIAID NIH HHS P30 AI110527NIAID NIH HHS R01 AI136740NIAID NIH HHS R01 AI170228NIAID NIH HHS R25 AI164610NIA NIH HHS K01 AG062757NIA NIH HHS P30 AG072947NIA NIH HHS R00 AG065445NICHD NIH HHS R01 HD074711NICHD NIH HHS R01 HD090061NIDA NIH HHS R01 DA057204NIDDK NIH HHS P30 DK020593NIDDK NIH HHS R00 DK120876NIDDK NIH HHS R01 DK133698NIDDK NIH HHS R21 DK119879NIDDK NIH HHS T32 DK007563NIGMS NIH HHS P50 GM115305NIGMS NIH HHS RC2 GM092618NIH HHS S10 OD017985NINDS NIH HHS R01 NS032830
6 · The paper itself

Abstract

The liver, the largest internal organ and a metabolic hub, undergoes significant declines due to aging, affecting mitochondrial function and increasing the risk of systemic liver diseases. How the mitochondrial three-dimensional (3D) structure changes in the liver across aging, and the biological mechanisms regulating such changes confers remain unclear. In this study, we employed Serial Block Face-Scanning Electron Microscopy (SBF-SEM) to achieve high-resolution 3D reconstructions of murine liver mitochondria to observe diverse phenotypes and structural alterations that occur with age, marked by a reduction in size and complexity. We also show concomitant metabolomic and lipidomic changes in aged samples. Aged human samples reflected altered disease risk. To find potential regulators of this change, we examined the Mitochondrial Contact Site and Cristae Organizing System (MICOS) complex, which plays a crucial role in maintaining mitochondrial architecture. We observe that the MICOS complex is lost during aging, but not Sam50. Sam50 is a component of the sorting and assembly machinery (SAM) complex that acts in tandem with the MICOS complex to modulate cristae morphology. In murine models subjected to a high-fat diet, there is a marked depletion of the mitochondrial protein SAM50. This reduction in Sam50 expression may heighten the susceptibility to liver disease, as our human biobank studies corroborate that Sam50 plays a genetically regulated role in the predisposition to multiple liver diseases. We further show that changes in mitochondrial calcium dysregulation and oxidative stress accompany the disruption of the MICOS complex. Together, we establish that a decrease in mitochondrial complexity and dysregulated metabolism occur with murine liver aging. While these changes are partially be regulated by age-related loss of the MICOS complex, the confluence of a murine high-fat diet can also cause loss of Sam50, which contributes to liver diseases. In summary, our study reveals potential regulators that affect age-related changes in mitochondrial structure and metabolism, which can be targeted in future therapeutic techniques.

Indexed as

3D StructureAgingLiver DiseaseMetabolismMICOS ComplexMitochondria

Identifiers

PMID38979162
PMCPMC11230271

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