TY - JOUR
T1 - 3D reconstruction of murine mitochondria reveals changes in structure during aging linked to the MICOS complex
AU - Vue, Zer
AU - Garza-Lopez, Edgar
AU - Neikirk, Kit
AU - Katti, Prasanna
AU - Vang, Larry
AU - Beasley, Heather
AU - Shao, Jianqiang
AU - Marshall, Andrea G.
AU - Crabtree, Amber
AU - Murphy, Alexandria C.
AU - Jenkins, Brenita C.
AU - Prasad, Praveena
AU - Evans, Chantell
AU - Taylor, Brittany
AU - Mungai, Margaret
AU - Killion, Mason
AU - Stephens, Dominique
AU - Christensen, Trace A.
AU - Lam, Jacob
AU - Rodriguez, Benjamin
AU - Phillips, Mark A.
AU - Daneshgar, Nastaran
AU - Koh, Ho Jin
AU - Koh, Alice
AU - Davis, Jamaine
AU - Devine, Nina
AU - Saleem, Mohammad
AU - Scudese, Estevão
AU - Arnold, Kenneth Ryan
AU - Vanessa Chavarin, Valeria
AU - Daniel Robinson, Ryan
AU - Chakraborty, Moumita
AU - Gaddy, Jennifer A.
AU - Sweetwyne, Mariya T.
AU - Wilson, Genesis
AU - Zaganjor, Elma
AU - Kezos, James
AU - Dondi, Cristiana
AU - Reddy, Anilkumar K.
AU - Glancy, Brian
AU - Kirabo, Annet
AU - Quintana, Anita M.
AU - Dai, Dao Fu
AU - Ocorr, Karen
AU - Murray, Sandra A.
AU - Damo, Steven M.
AU - Exil, Vernat
AU - Riggs, Blake
AU - Mobley, Bret C.
AU - Gomez, Jose A.
AU - McReynolds, Melanie R.
AU - Hinton, Antentor
N1 - Publisher Copyright:
© 2023 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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U2 - 10.1111/acel.14009
DO - 10.1111/acel.14009
M3 - Article
C2 - 37960952
AN - SCOPUS:85176954269
SN - 1474-9718
VL - 22
JO - Aging cell
JF - Aging cell
IS - 12
M1 - e14009
ER -