Quantitative assessment of morphological changes in lipid droplets and lipid–mito interactions with aging in brown adipose

Author:

Crabtree Amber12,Neikirk Kit1,Pinette Julia A.1,Whiteside Aaron1,Shao Bryanna1,Bedenbaugh Jessica1,Vue Zer1,Vang Larry1,Le Han1,Demirci Mert3,Ahmad Taseer45,Owens Trinity Celeste1,Oliver Ashton1,Zeleke Faben1,Beasley Heather K.1,Lopez Edgar Garza6,Scudese Estevão1,Rodman Taylor1,Kabugi Kinuthia1,Koh Alice1,Navarro Suzanne1,Lam Jacob6,Kirk Ben6,Mungai Margaret16,Sweetwyne Mariya7,Koh Ho‐Jin8,Zaganjor Elma1,Damo Steven M.9,Gaddy Jennifer A.1011,Kirabo Annet4ORCID,Murray Sandra A.12,Cooper Anthonya12,Williams Clintoria13,McReynolds Melanie R.1415,Marshall Andrea G.1,Hinton Antentor1ORCID

Affiliation:

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

2. The Frist Center for Autism and Innovation Vanderbilt University Nashville Tennessee USA

3. Department of Medicine, Division Nephrology and Hypertension Vanderbilt University Medical Center Nashville Tennessee USA

4. Department of Medicine, Division of Clinical Pharmacology Vanderbilt University Medical Center Nashville Tennessee USA

5. Department of Pharmacology, College of Pharmacy University of Sargodha Sargodha Punjab Pakistan

6. Department of Internal Medicine University of Iowa Iowa City Iowa USA

7. Department of Laboratory Medicine and Pathology University of Washington Seattle Washington USA

8. Department of Biological Sciences Tennessee State University Nashville Tennessee USA

9. Department of Life and Physical Sciences Fisk University Nashville Tennessee USA

10. Division of Infectious Diseases Vanderbilt University School of Medicine Nashville Tennessee USA

11. Tennessee Valley Healthcare Systems U.S. Department of Veterans Affairs Nashville Tennessee USA

12. Department of Cell Biology, School of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA

13. Department of Neuroscience, Cell Biology and Physiology Wright State University Dayton Ohio USA

14. Department of Biochemistry and Molecular Biology Pennsylvania State University University Park Pennsylvania USA

15. Huck Institutes of the Life Sciences Pennsylvania State University University Park Pennsylvania USA

Abstract

AbstractThe physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LDs) within the brown adipocytes and a high abundance of iron‐containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle‐to‐organelle contacts. For example, the contact sites that mediate mitochondria–LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids. Aging is associated with mitochondrial dysfunction, and previous studies show that there are changes in mitochondrial structure and the proteins that modulate organelle contact sites. However, how mitochondria–LD interactions change with aging has yet to be fully clarified. Therefore, we sought to define age‐related changes in LD morphology and mitochondria–lipid interactions in BAT. We examined the three‐dimensional morphology of mitochondria and LDs in young (3‐month) and aged (2‐year) murine BAT using serial block face‐scanning electron microscopy and the Amira program for segmentation, analysis, and quantification. Our analyses showed reductions in LD volume, area, and perimeter in aged samples in comparison to young samples. Additionally, we observed changes in LD appearance and type in aged samples compared to young samples. Notably, we found differences in mitochondrial interactions with LDs, which could implicate that these contacts may be important for energetics in aging. Upon further investigation, we also found changes in mitochondrial and cristae structure for the mitochondria interacting with LDs. Overall, these data define the nature of LD morphology and organelle–organelle contacts during aging and provide insight into LD contact site changes that interconnect biogerontology with mitochondrial function, metabolism, and bioactivity in aged BAT.

Publisher

Wiley

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