3D reconstruction of murine mitochondria reveals changes in structure during aging linked to the MICOS complex

Zer Vue, Edgar Garza-Lopez, Kit Neikirk, Prasanna Katti, Larry Vang, Heather Beasley, Jianqiang Shao, Andrea G. Marshall, Amber Crabtree, Alexandria C. Murphy, Brenita C. Jenkins, Praveena Prasad, Chantell Evans, Brittany Taylor, Margaret Mungai, Mason Killion, Dominique Stephens, Trace A. Christensen, Jacob Lam, Benjamin RodriguezMark A. Phillips, Nastaran Daneshgar, Ho Jin Koh, Alice Koh, Jamaine Davis, Nina Devine, Mohammad Saleem, Estevão Scudese, Kenneth Ryan Arnold, Valeria Vanessa Chavarin, Ryan Daniel Robinson, Moumita Chakraborty, Jennifer A. Gaddy, Mariya T. Sweetwyne, Genesis Wilson, Elma Zaganjor, James Kezos, Cristiana Dondi, Anilkumar K. Reddy, Brian Glancy, Annet Kirabo, Anita M. Quintana, Dao Fu Dai, Karen Ocorr, Sandra A. Murray, Steven M. Damo, Vernat Exil, Blake Riggs, Bret C. Mobley, Jose A. Gomez, Melanie R. McReynolds, Antentor Hinton

Research output: Contribution to journalArticlepeer-review

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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.

Original languageEnglish (US)
Article numbere14009
JournalAging cell
Issue number12
StatePublished - Dec 2023

All Science Journal Classification (ASJC) codes

  • Aging
  • Cell Biology

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