ArticleAging cell2023
3D reconstruction of murine mitochondria reveals changes in structure during aging linked to the MICOS complex.
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Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44citing papers in PubMed
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Who cites it
44 citing papers in PubMed, 55 citations in OpenAlex.
- POU2F1 promotes hypertensive cardiac fibrosis by regulating mitochondrial homeostasis through PINK1/Parkin‑dependent mitophagy.Molecular medicine reports · 2026Article
- Inflammaging-associated mitochondrial degeneration occurs in hypoglossal motor neurons prior to tongue muscle.GeroScience · 2026Article
- 3D EM uncovers mitochondrial network remodeling in residual triple negative breast cancer after conventional chemotherapy treatments.iScience · 2026Article
- Aging Remodels Mitochondrial Architecture Across the Male Reproductive Axis.Research square · 2026Article
- TACO1 regulates mitochondrial adaptation in hypertension-induced cardiac remodeling and heart failure.Research square · 2026Article
- The MICOS Complex Regulates Mitochondrial Structure and Oxidative Stress During Age-Dependent Structural Deficits in the Kidney.Aging cell · 2026Article
- Structural and mitochondrial dendritic degenerations in old hypoglossal motor neurons.GeroScience · 2026Article
- ATF4 Coordinates Transcriptomic and Structural Adaptations in Aging Muscle.bioRxiv : the preprint server for biology · 2026Article
- Radical Revelations: The Interplay of Nitrosative Stress, the Endocannabinoid System, and Treatment of Age-Related Disorders.International journal of molecular sciences · 2026Review
- The MICOS Complex Regulates Mitochondrial Structure and Oxidative Stress During Age-Dependent Structural Deficits in the Kidney.bioRxiv : the preprint server for biology · 2026Article
- Review
- CHCHD3(MIC19): mitochondrial cristae structure regulation and disease associations.Frontiers in molecular biosciences · 2026Review
- Pharmacological inhibition of MCL-1 disrupts mitochondrial cristae and depletes the human neural progenitor cell pool.bioRxiv : the preprint server for biology · 2025Article
- The role of MICOS in modulating mitochondrial dynamics and structural changes in vulnerable regions of Alzheimer's Disease.bioRxiv : the preprint server for biology · 2025Article
- Narrative review of mitochondrial dysfunction in aging-related salt-sensitive hypertension: outcomes, mechanisms, and therapeutic implications.Aging advances · 2025Article
- Molecular Framework of the Onset and Progression of Skeletal Muscle Aging.International journal of molecular sciences · 2025Review
- Resilience of the mitochondrial reticulum in aging.American journal of physiology. Endocrinology and metabolism · 2025Article
- Promoting mitochondrial fusion is protective against cancer-induced muscle detriments in males and females.BMC cancer · 2025Article
- Melatonin protects against sarcopenia in middle-aged mice.Histology and histopathology · 2025Article
- Metabolomic characterization of unintentional weight loss among community-dwelling older Black and White men and women.Aging cell · 2025Article
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Authors and funding
52 authors at 20 institutions in 2 countries.
Zer VueDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.
Edgar Garza-LopezDepartment of Internal Medicine, University of Iowa, Iowa, Iowa City, USA.
Kit NeikirkDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.
Prasanna KattiNational Heart, Lung and Blood Institute, National Institutes of Health, Maryland, Bethesda, USA.
Larry VangDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.
Heather BeasleyDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.
Jianqiang ShaoCentral Microscopy Research Facility, University of Iowa, Iowa, Iowa City, USA.
Andrea G MarshallDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.
Amber CrabtreeDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.
Alexandria C MurphyDepartment of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, Pennsylvania, State College, USA.
Brenita C JenkinsDepartment of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, Pennsylvania, State College, USA.
Praveena PrasadDepartment of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, Pennsylvania, State College, USA.
Chantell EvansDepartment of Cell Biology, Duke University School of Medicine, North Carolina, Durham, USA.
Brittany TaylorJ. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Florida, Gainesville, USA.
Margaret MungaiDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.
Mason KillionDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.ORCID 0009-0008-0874-9979
Dominique StephensDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.
Trace A ChristensenMicroscopy and Cell Analysis Core Facility, Mayo Clinic, Minnesota, Rochester, USA.
Jacob LamDepartment of Internal Medicine, University of Iowa, Iowa, Iowa City, USA.
Benjamin RodriguezDepartment of Internal Medicine, University of Iowa, Iowa, Iowa City, USA.
Mark A PhillipsDepartment of Integrative Biology, Oregon State University, Oregon, Corvallis, USA.
Nastaran DaneshgarDepartment of Integrative Biology, Oregon State University, Oregon, Corvallis, USA.
Ho-Jin KohDepartment of Biological Sciences, Tennessee State University, Tennessee, Nashville, USA.
Alice KohDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.
Jamaine DavisDepartment of Biochemistry, Cancer Biology, Neuroscience, and Pharmacology, Meharry Medical College, Tennessee, Nashville, USA.
Nina DevineDepartment of Integrative Biology, Oregon State University, Oregon, Corvallis, USA.
Mohammad SaleemDepartment of Medicine, Vanderbilt University Medical Center, Tennessee, Nashville, USA.
Estevão ScudeseLaboratory of Biosciences of Human Motricity (LABIMH) of the Federal University of State of Rio de Janeiro (UNIRIO), Rio de Janeiro, Brazil.
Kenneth Ryan ArnoldDepartment of Ecology and Evolutionary Biology, University of California at Irvine, California, Irvine, USA.
Valeria Vanessa ChavarinDepartment of Ecology and Evolutionary Biology, University of California at Irvine, California, Irvine, USA.
Ryan Daniel RobinsonDepartment of Ecology and Evolutionary Biology, University of California at Irvine, California, Irvine, USA.
Moumita ChakrabortyDepartment of Integrative Biology, Oregon State University, Oregon, Corvallis, USA.
Jennifer A GaddyDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.
Mariya T SweetwyneDepartment of Laboratory Medicine and Pathology, University of Washington, Washington, Seattle, USA.
Genesis WilsonDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.ORCID 0000-0001-7367-2324
Elma ZaganjorDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.
James KezosSanford Burnham Prebys Medical Discovery Institute, California, La Jolla, USA.
Cristiana DondiSanford Burnham Prebys Medical Discovery Institute, California, La Jolla, USA.
Anilkumar K ReddyDepartment of Medicine, Baylor College of Medicine, Texas, Houston, USA.
Brian GlancyNational Heart, Lung and Blood Institute, National Institutes of Health, Maryland, Bethesda, USA.
Annet KiraboDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.
Anita M QuintanaDepartment of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, Texas, El Paso, USA.
Dao-Fu DaiDepartment of Pathology, University of Johns Hopkins School of Medicine, Maryland, Baltimore, USA.
Karen OcorrSanford Burnham Prebys Medical Discovery Institute, California, La Jolla, USA.ORCID 0000-0003-2593-0119
Sandra A MurrayDepartment of Cell Biology, School of Medicine, University of Pittsburgh, Pennsylvania, Pittsburgh, USA.
Steven M DamoDepartment of Life and Physical Sciences, Fisk University, Tennessee, Nashville, USA.
Vernat ExilDepartment of Pediatrics, Carver College of Medicine, University of Iowa, Iowa, Iowa City, USA.ORCID 0000-0001-5935-4039
Blake RiggsDepartment of Biology, San Francisco State University, California, San Francisco, USA.
Bret C MobleyDepartment of Pathology, Vanderbilt University Medical Center, Tennessee, Nashville, USA.
Jose A GomezDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.
Melanie R McReynoldsDepartment of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, Pennsylvania, State College, USA.
Antentor HintonDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Tennessee, Nashville, USA.ORCID 0000-0002-7730-952X
Vanderbilt University · USUniversity of Iowa · USOregon State University · USPennsylvania State University · USSanford Burnham Prebys Medical Discovery Institute · USUniversity of California, Irvine · USNational Institutes of Health · USVanderbilt University Medical Center · USBaylor College of Medicine · USDuke University · USJohns Hopkins University · USMayo Clinic · USMeharry Medical College · USSan Francisco State University · USTennessee State University · USThe University of Texas at El Paso · USUniversidade Católica de Petrópolis · BRUniversity of Florida · USUniversity of Pittsburgh · USUniversity of Washington · US
Funding
VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7MThe Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4MTranslational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9MVanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ALVIN C POWERS · 2012 to 2026
$29.3MMULTIDISCIPLINARY TRAINING IN MOLECULAR ENDOCRINOLOGYT32DK007563 · NIDDK · VANDERBILT UNIVERSITY · PI Richard M O'Brien · 1988 to 2026
$15.9MPRIDE: Functional and Translational Genomics of Blood DisordersR25HL106365 · NHLBI · AUGUSTA UNIVERSITY · PI PACE, BETTY SUE · 2010 to 2024
$5.2MENaC regulation and its role in blood pressure homeostasisR01HL147818 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Annet Kirabo, Thomas R Kleyman · 2019 to 2026
$4.6MIntegrated Training in Engineering and DiabetesT32DK101003 · NIDDK · VANDERBILT UNIVERSITY · PI Jamey D. Young · 2014 to 2026
$3.9MImmune Mechanisms of Salt-Sensitive hypertensionR01HL144941 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI KIRABO, ANNET · 2021 to 2025
$3.0MDetermining the contribution of zinc deficiency to perinatal Group B Streptococcus infectionsR01HD090061 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ARONOFF, DAVID M, GADDY, JENNIFER A · 2017 to 2021
$2.5MUCSD Leading the Advancement of Underrepresented Neuroscientists for Change (LAUNCH) Faculty Development ProgramR25NS117367 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Victoria B Risbrough, Joann Trejo · 2020 to 2026
$1.6MMitochondrial Protection to Derive Expanded Aged Renal Glomerular Progenitor CellsK01AG062757 · NIA · UNIVERSITY OF WASHINGTON · PI SWEETWYNE, MARIYA TS'ANA · 2019 to 2023
$619kBLRD VA I01 BX005352Howard Hughes Medical Institute GT15655NCATS NIH HHS UL1 TR000445NCRR NIH HHS Grant 2 UL1 TR000445-06NCRR NIH HHS RR024975-01NCRR NIH HHS UL1 RR024975NHLBI NIH HHS R01 HL144941NHLBI NIH HHS R01 HL147818NHLBI NIH HHS R03 HL155041NHLBI NIH HHS R25 HL106365NIA NIH HHS K01 AG062757NICHD NIH HHS R01 HD090061NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P30 DK058404NIDDK NIH HHS T32 DK007563NIDDK NIH HHS T32 DK101003NIH HHS 5R25HL106365-12NIH HHS DK007563NIH HHS DK101003NIH HHS HD090061NIH HHS K01AG062757NIH HHS R01HL144941NIH HHS R01HL147818NIH HHS R03HL155041NINDS NIH HHS R25 NS117367
Abstract
During aging, muscle gradually undergoes sarcopenia, the loss of function associated with loss of mass, strength, endurance, and oxidative capacity. However, the 3D structural alterations of mitochondria associated with aging in skeletal muscle and cardiac tissues are not well described. Although mitochondrial aging is associated with decreased mitochondrial capacity, the genes responsible for the morphological changes in mitochondria during aging are poorly characterized. We measured changes in mitochondrial morphology in aged murine gastrocnemius, soleus, and cardiac tissues using serial block-face scanning electron microscopy and 3D reconstructions. We also used reverse transcriptase-quantitative PCR, transmission electron microscopy quantification, Seahorse analysis, and metabolomics and lipidomics to measure changes in mitochondrial morphology and function after loss of mitochondria contact site and cristae organizing system (MICOS) complex genes, Chchd3, Chchd6, and Mitofilin. We identified significant changes in mitochondrial size in aged murine gastrocnemius, soleus, and cardiac tissues. We found that both age-related loss of the MICOS complex and knockouts of MICOS genes in mice altered mitochondrial morphology. Given the critical role of mitochondria in maintaining cellular metabolism, we characterized the metabolomes and lipidomes of young and aged mouse tissues, which showed profound alterations consistent with changes in membrane integrity, supporting our observations of age-related changes in muscle tissues. We found a relationship between changes in the MICOS complex and aging. Thus, it is important to understand the mechanisms that underlie the tissue-dependent 3D mitochondrial phenotypic changes that occur in aging and the evolutionary conservation of these mechanisms between Drosophila and mammals.
Indexed as
Imaging, Three-DimensionalMitochondria Associated MembranesAnimalsDNA, MitochondrialMammalsMiceMitochondriaMitochondrial MembranesMitochondrial ProteinsDNA, MitochondrialMitochondrial Proteins3D morphometryagingDrosophilaMICOSmitochondriamitochondrial diseasemitochondrionreconstructionreticulumserial block-face SEMskeletal muscle
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