Journal article
Three-Dimensional Mitochondria Reconstructions of Murine Cardiac Muscle Changes in Size Across Aging
American journal of physiology. Heart and circulatory physiology, Vol.325(5), pp.H965-H982
11/01/2023
DOI: 10.1152/ajpheart.00202.2023
PMCID: PMC10977873
PMID: 37624101
Abstract
With sparse treatment options, cardiac disease remains a significant cause of death among humans. As a person ages, mitochondria break down and the heart becomes less efficient. Heart failure is linked to many mitochondria-associated processes, including endoplasmic reticulum stress, mitochondrial bioenergetics, insulin signaling, autophagy, and oxidative stress. The roles of key mitochondrial complexes that dictate the ultrastructure, such as the mitochondrial contact site and cristae organizing system (MICOS), in aging cardiac muscle are poorly understood. To better understand the cause of age-related alteration in mitochondrial structure in cardiac muscle, we used transmission electron microscopy (TEM) and serial block facing-scanning electron microscopy (SBF-SEM) to quantitatively analyze the 3D networks in cardiac muscle samples of male mice at aging intervals of 3 months, 1 year, and 2 years. Here, we present the loss of cristae morphology, the inner folds of the mitochondria, across age. In conjunction with this, the 3D volume of mitochondria decreased. These findings mimicked observed phenotypes in murine cardiac fibroblasts with CRISPR/Cas9 knockout of Mitofilin, Chchd3, Chchd6 (some members of the MICOS complex), and Opa1, which showed poorer oxidative consumption rate and mitochondria with decreased mitochondrial length and volume. In combination, these data show the need to explore if loss of the MICOS complex in the heart may be involved in age-associated mitochondrial and cristae structural changes.
Details
- Title: Subtitle
- Three-Dimensional Mitochondria Reconstructions of Murine Cardiac Muscle Changes in Size Across Aging
- Creators
- Zer Vue - Vanderbilt UniversityKit Neikirk - Vanderbilt UniversityLarry Vang - Vanderbilt UniversityEdgar Garza-Lopez - University of Iowa, United StatesTrace A. Christensen - Mayo ClinicJianqiang Shao - University of IowaJacob Lam - University of IowaHeather K. Beasley - Vanderbilt UniversityAndrea G. Marshall - Vanderbilt UniversityAmber Crabtree - Vanderbilt UniversityJosephs Anudokem - Meharry Medical CollegeBenjamin Rodriguez - Vanderbilt UniversityBenjamin Kirk - University of Iowa, United StatesSerif Bacevac - University of IowaTaylor Barongan - Vanderbilt UniversityBryanna Shao - Vanderbilt UniversityDominique C. Stephens - Vanderbilt UniversityKinuthia Kabugi - Vanderbilt UniversityHo-Jin Koh - Tennessee State UniversityAlice Koh - Vanderbilt UniversityChantell S. Evans - Duke University School of MedicineBrittany Taylor - University of Florida, United StatesAnilkumar K. Reddy - Baylor College of MedicineTyne Miller-Fleming - Vanderbilt UniversityKy'Era V. Actkins - Vanderbilt University Medical CenterElma Zaganjor - Vanderbilt UniversityNastaran Daneshgar - University of IowaSandra A. Murray - University of PittsburghBret C. Mobley - Vanderbilt University Medical CenterSteven Damo - Fisk UniversityJennifer A. Gaddy - Vanderbilt University Medical CenterBlake Riggs - San Francisco State UniversityCelestine Wanjalla - Vanderbilt University Medical CenterAnnet Kirabo - Vanderbilt University Medical CenterMelanie McReynolds - Pennsylvania State UniversityJose A. Gomez - Vanderbilt University Medical CenterMark A. Phillips - Oregon State UniversityVernat Exil - Monroe Carell Jr. Children's HospitalDao-Fu Dai - University of IowaAntentor Hinton - Vanderbilt University
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.325(5), pp.H965-H982
- DOI
- 10.1152/ajpheart.00202.2023
- PMID
- 37624101
- PMCID
- PMC10977873
- NLM abbreviation
- Am J Physiol Heart Circ Physiol
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Publisher
- American Physiological Society
- Grant note
- name: CZI Science Diversity Leadership, award: 2022-253614 (from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation); name: United Negro College Fund/Bristol-Myers Squibb, award: E.E. Just Faculty Fund; name: Vanderbilt Diabetes and Research Training Center for DRTC Alzheimer’s Disease Pilot & Feasibility Program; name: CZI Science Diversity Leadership, award: 2022-253529 (from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation); name: United Negro College Fund/Bristol-Myers Squibb, award: E.E. Just Postgraduate Fellowship in Life sciences Fellowship; DOI: 10.13039/100000861, name: Burroughs Wellcome Fund, award: 1022376 (Postdoctoral Enrichment Program); DOI: 10.13039/100000861, name: Burroughs Wellcome Fund, award: Ad-hoc Award; DOI: 10.13039/100000861, name: Burroughs Wellcome Fund, award: Career Award at the Scientific Interface (CASI Award); DOI: 10.13039/100000861, name: Burroughs Wellcome Fund, award: 1022355 (Postdoctoral Enrichment Program); DOI: 10.13039/100000071, name: HHS | NIH | National Institute of Child Health and Human Development, award: R01HD090061; DOI: 10.13039/100000062, name: HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases, award: DK101003 (Integrated Training in Engineering and Diabetes); DOI: 10.13039/100000062, name: HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases, award: DK007563 (Multidisciplinary Training in Molecular Endocrinology); DOI: 10.13039/100000057, name: HHS | NIH | National Institute of General Medical Sciences, award: T32 5T32GM133353; DOI: 10.13039/100000002, name: HHS | National Institutes of Health, award: Small Research Pilot Subawardto 5R25HL106365-12 from the National Institutes of Health PRIDE Program, DK02059; DOI: 10.13039/100000001, name: National Science Foundation, award: MCB 2011577I; DOI: 10.13039/100000001, name: National Science Foundation, award: EES2112556, EES1817282, and MCB1955975; DOI: 10.13039/100000738, name: U.S. Department of Veterans Affairs, award: I01 BX005352 (Research Grant)
- Language
- English
- Electronic publication date
- 08/25/2023
- Date published
- 11/01/2023
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984458105002771
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