Defining Mitochondrial Cristae Morphology Changes Induced by Aging in Brown Adipose Tissue

Crabtree, A.; Neikirk, K.; Marshall, A.; Vang, L.; Stephens, D.; Shao, B.; Garza-Lopez, E.; Lam, J.; Rodriguez, B.; Mungai, M.; Stanley, J.; Dean, D.; Gaddy, J.; Scudese, E.; Sweetwyne, M.; Davis, J.; Zaganjor, E.; Murray, S.; Katti, P.; Damo, S.; Vue, Z.; Hinton, A.

doi:10.1101/2023.05.12.540609

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bioRxiv · 10.1101/2023.05.12.540609

Defining Mitochondrial Cristae Morphology Changes Induced by Aging in Brown Adipose Tissue

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Abstract

Mitochondria are required for energy production and even give brown adipose tissue (BAT) its characteristic color due to their high iron content and abundance. The physiological function and bioenergetic capacity of mitochondria are connected to the structure, folding, and organization of its inner-membrane cristae. During the aging process, mitochondrial dysfunction is observed, and the regulatory balance of mitochondrial dynamics is often disrupted, leading to increased mitochondrial fragmentation in aging cells. Therefore, we hypothesized that significant morphological changes in BAT mitochondria and cristae would be present with aging. We developed a quantitative three-dimensional (3D) electron microscopy approach to map cristae network organization in mouse BAT to test this hypothesis. Using this methodology, we investigated the 3D morphology of mitochondrial cristae in adult (3-month) and aged (2-year) murine BAT tissue via serial block face-scanning electron microscopy (SBF-SEM) and 3D reconstruction software for manual segmentation, analysis, and quantification. Upon investigation, we found increases in mitochondrial volume, surface area, and complexity and decreased sphericity in aged BAT, alongside significant decreases in cristae volume, area, perimeter, and score. Overall, these data define the nature of the mitochondrial structure in murine BAT across aging. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/540609v2_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@96099borg.highwire.dtl.DTLVardef@50b4f4org.highwire.dtl.DTLVardef@983092org.highwire.dtl.DTLVardef@19ceb9b_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO Overview of serial block facing-scanning electron microscopy (SBF-SEM) workflow, data segmentation, and 3D analysis of mitochondria using Amira software for murine interscapular BAT. C_FIG

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Crabtree, A., Neikirk, K., Marshall, A., Vang, L., Stephens, D., Shao, B., Garza-Lopez, E., Lam, J., Rodriguez, B., Mungai, M., Stanley, J., Dean, D., Gaddy, J., Scudese, E., Sweetwyne, M., Davis, J., Zaganjor, E., Murray, S., Katti, P., Damo, S., Vue, Z., Hinton, A.. 2023-05-14. Defining Mitochondrial Cristae Morphology Changes Induced by Aging in Brown Adipose Tissue. https://doi.org/10.1101/2023.05.12.540609

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