Journal article
3D reconstruction of murine mitochondria reveals changes in structure during aging linked to the MICOS complex
Aging cell, Vol.22(12), e14009
12/2023
DOI: 10.1111/acel.14009
PMCID: PMC10726809
PMID: 37960952
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.
Details
- Title: Subtitle
- 3D reconstruction of murine mitochondria reveals changes in structure during aging linked to the MICOS complex
- Creators
- Zer Vue - Vanderbilt UniversityEdgar Garza-Lopez - University of IowaKit Neikirk - Vanderbilt UniversityPrasanna Katti - National Heart Lung and Blood InstituteLarry Vang - Vanderbilt UniversityHeather Beasley - Vanderbilt UniversityJianqiang Shao - University of IowaAndrea G Marshall - Vanderbilt UniversityAmber Crabtree - Vanderbilt UniversityAlexandria C Murphy - Pennsylvania State UniversityBrenita C Jenkins - Pennsylvania State UniversityPraveena Prasad - Pennsylvania State UniversityChantell Evans - Duke UniversityBrittany Taylor - University of FloridaMargaret Mungai - Vanderbilt UniversityMason Killion - Vanderbilt UniversityDominique Stephens - Vanderbilt UniversityTrace A Christensen - Mayo ClinicJacob Lam - University of IowaBenjamin Rodriguez - University of IowaMark A Phillips - Oregon State UniversityNastaran Daneshgar - Oregon State UniversityHo-Jin Koh - Tennessee State UniversityAlice Koh - Vanderbilt UniversityJamaine Davis - Meharry Medical CollegeNina Devine - Oregon State UniversityMohammad Saleem - Vanderbilt University Medical CenterEstevão Scudese - Universidade Federal do Estado do Rio de JaneiroKenneth Ryan Arnold - University of California, IrvineValeria Vanessa Chavarin - Department of Ecology and Evolutionary Biology, University of California at Irvine, California, Irvine, USARyan Daniel Robinson - Department of Ecology and Evolutionary Biology, University of California at Irvine, California, Irvine, USAMoumita Chakraborty - Oregon State UniversityJennifer A Gaddy - Vanderbilt UniversityMariya T Sweetwyne - University of WashingtonGenesis Wilson - Vanderbilt UniversityElma Zaganjor - Vanderbilt UniversityJames Kezos - Sanford Burnham Prebys Medical Discovery InstituteCristiana Dondi - Sanford Burnham Prebys Medical Discovery InstituteAnilkumar K Reddy - Baylor College of MedicineBrian Glancy - National Heart Lung and Blood InstituteAnnet Kirabo - Vanderbilt University Medical CenterAnita M Quintana - The University of Texas at El PasoDao-Fu Dai - Department of Pathology, University of Johns Hopkins School of Medicine, Maryland, Baltimore, USAKaren Ocorr - Sanford Burnham Prebys Medical Discovery InstituteSandra A Murray - University of PittsburghSteven M Damo - Vanderbilt UniversityVernat Exil - University of IowaBlake Riggs - San Francisco State UniversityBret C Mobley - Vanderbilt University Medical CenterJose A Gomez - Vanderbilt University Medical CenterMelanie R McReynolds - Pennsylvania State UniversityAntentor Hinton Jr - Vanderbilt University
- Resource Type
- Journal article
- Publication Details
- Aging cell, Vol.22(12), e14009
- DOI
- 10.1111/acel.14009
- PMID
- 37960952
- PMCID
- PMC10726809
- NLM abbreviation
- Aging Cell
- ISSN
- 1474-9718
- eISSN
- 1474-9726
- Grant note
- DK101003 / NIH HHS Grant 2 UL1 TR000445-06 / NCRR NIH HHS P30 DK058404 / NIDDK NIH HHS UL1 RR024975 / NCRR NIH HHS RR024975-01 / NCRR NIH HHS P30 DK020593 / NIDDK NIH HHS R01HL144941 / NIH HHS R01 HL144941 / NHLBI NIH HHS UL1 TR000445 / NCATS NIH HHS K01AG062757 / NIH HHS HD090061 / NIH HHS GT15655 / Howard Hughes Medical Institute R25 HL106365 / NHLBI NIH HHS 5R25HL106365-12 / NIH HHS T32 DK007563 / NIDDK NIH HHS DK007563 / NIH HHS R01HL147818 / NIH HHS R03HL155041 / NIH HHS R25 NS117367 / NINDS NIH HHS I01 BX005352 / BLRD VA
- Language
- English
- Date published
- 12/2023
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9984643651102771
Metrics
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