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

Author:

Crabtree Amber1,Neikirk Kit1,Marshall Andrea G.1,Vang Larry1,Whiteside Aaron J.1,Williams Qiana1,Altamura Christopher T.1,Owens Trinity Celeste1,Stephens Dominique1,Shao Bryanna1,Koh Alice1,Killion Mason1,Lopez Edgar Garza2,Lam Jacob2,Rodriguez Ben2,Mungai Margaret2,Stanley Jade1,Dean E. Danielle13,Koh Ho‐Jin4,Gaddy Jennifer A.56,Scudese Estevão78,Sweetwyne Mariya T.9,Davis Jamaine10,Zaganjor Elma1,Murray Sandra A.11,Katti Prasanna12,Damo Steven M.1314,Vue Zer1,Hinton Antentor1ORCID

Affiliation:

1. Department of Molecular Physiology and Biophysics Vanderbilt University Nashville TN 37232 USA

2. Department of Internal Medicine University of Iowa Iowa City IA 52242 USA

3. Division of Diabetes, Endocrinology, and Metabolism Department of Medicine Vanderbilt University Medical Center Nashville TN 37232 USA

4. Department of Medicine Vanderbilt University Medical Center Nashville TN 37232 USA

5. Department of Biological Sciences Tennessee State University Nashville TN 37209 USA

6. Tennessee Valley Healthcare Systems U.S. Department of Veterans Affairs Nashville TN 37232 USA

7. Laboratory of Biosciences of Human Motricity (LABIMH) Federal University of State of Rio de Janeiro (UNIRIO) Rio de Janeiro 22290‐240 Brazil

8. Sport Sciences and Exercise Laboratory (LaCEE) Catholic University of Petrópolis (UCP) Rio de Janeiro 22290‐240 Brazil

9. Department of Laboratory Medicine and Pathology University of Washington Seattle WA 98195 USA

10. Department of Biochemistry Cancer Biology Neuroscience Pharmacology Meharry Medical College Nashville TN 37208 USA

11. Department of Cell Biology University of Pittsburgh Pittsburg PA 15261 USA

12. National Heart, Lung and Blood Institute National Institutes of Health 9000 Rockville Pike Bethesda MD 20892 USA

13. Department of Life and Physical Sciences Fisk University Nashville TN 37208 USA

14. Center for Structural Biology Vanderbilt University Nashville TN 37232 USA

Abstract

AbstractMitochondria 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, it is hypothesized that significant morphological changes in BAT mitochondria and cristae will be present with aging. A quantitative 3D electron microscopy approach is developed to map cristae network organization in mouse BAT to test this hypothesis. Using this methodology, the 3D morphology of mitochondrial cristae is investigated 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, an increase is found 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.

Funder

National Institutes of Health

National Science Foundation

Burroughs Wellcome Fund

Publisher

Wiley

Subject

General Medicine

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