ESPEYB18 11. Obesity and Weight Regulation Mechanism of the year (1 abstracts)
11.10. Intercellular mitochondria transfer to macrophages regulates white adipose tissue homeostasis and is impaired in obesity
Brestoff JR , Wilen CB , Moley JR , Li Y , Zou W , Malvin NP , Rowen MN , Saunders BT , Ma H , Mack MR , Hykes BL , Balce DR , Orvedahl A , Williams JW , Rohatgi N , Wang X , McAllaster MR , Handley SA , Kim BS , Doench JG , Zinselmeyer BH , Diamond MS , Virgin HW , Gelman AE & Teitelbaum SL
Yale School of Medicine, New Haven, Connecticut, USA. teitelbs@wustl.edu.
Cell Metab 2021;33(2): 270–282.e8. doi: https://doi.org/10.1016/j.cmet.2020.11.008
Brestoff et al. show, for the first time, that mitochondria are transferred from adipocytes to macrophages and that this event has an impact on systemic metabolic homeostasis.Within the last years, it has been demonstrated that cells are able to communicate with each other by the exchange of organelles, such as lysosomes and mitochondria, and this gained considerable interest in different fields of medicine. Intercellular exchange of mitochondria can take place by several mechanisms, including tunnelling microtubes, extracellular vesicles, or cell fusion (1). Moreover, mitochondria appear to be transported systemically as well, as they are frequently found in the circulation (2). Whether or not mitochondrial transfer takes place in the adipose tissue had not been investigated so far. The authors used a transplantation mouse model, in which mitochondria in the adipose tissue were specifically labelled. They showed a directed transfer of mitochondria from adipocytes to macrophages, which was dependent on the presence of heparan sulphate on the surface of macrophages. This transport was diminished in high-fat-diet (HDF) obesity, and conversely, inhibition of mitochondrial transfer resulted in metabolic dysfunction.
Overall, these findings clearly demonstrates that adipocyte-macrophage exchange is relevant for obesity development. Still, it would have been desirable to unravel the mechanism of mitochondrial exchange in more detail. As the fluorescent images implicate, it seems that mitochondria are taken up into macrophages by endocytosis, which is the major function of these cells. It would have been interesting to know the mechanisms that prevent macrophages from degrading mitochondria, and instead utilise them. Further research might address whether intercellular organelle transport takes place in humans as well. The presence of mitochondria in the bloodstream (2) suggests that this might be true, and opens up new avenues for the study of intercellular or inter-organ communication in humans.
References: 1. Murray, L. M. A. & Krasnodembskaya, A. D. Concise Review: Intercellular Communication Via Organelle Transfer in the Biology and Therapeutic Applications of Stem Cells. Stem Cells 37, 14–25 (2019).2. Al Amir Dache, Z. et al. Blood contains circulating cell-free respiratory competent mitochondria. FASEB J. 34, 3616–3630 (2020).
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ESPE Yearbook of Paediatric Endocrinology
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