| Literature DB >> 33278339 |
Jonathan R Brestoff1, Craig B Wilen2, John R Moley1, Yongjia Li1, Wei Zou1, Nicole P Malvin1, Marina N Rowen1, Brian T Saunders1, Hongming Ma3, Madison R Mack4, Barry L Hykes1, Dale R Balce5, Anthony Orvedahl6, Jesse W Williams1, Nidhi Rohatgi1, Xiaoyan Wang1, Michael R McAllaster1, Scott A Handley1, Brian S Kim7, John G Doench8, Bernd H Zinselmeyer1, Michael S Diamond9, Herbert W Virgin10, Andrew E Gelman11, Steven L Teitelbaum12.
Abstract
Recent studies suggest that mitochondria can be transferred between cells to support the survival of metabolically compromised cells. However, whether intercellular mitochondria transfer occurs in white adipose tissue (WAT) or regulates metabolic homeostasis in vivo remains unknown. We found that macrophages acquire mitochondria from neighboring adipocytes in vivo and that this process defines a transcriptionally distinct macrophage subpopulation. A genome-wide CRISPR-Cas9 knockout screen revealed that mitochondria uptake depends on heparan sulfates (HS). High-fat diet (HFD)-induced obese mice exhibit lower HS levels on WAT macrophages and decreased intercellular mitochondria transfer from adipocytes to macrophages. Deletion of the HS biosynthetic gene Ext1 in myeloid cells decreases mitochondria uptake by WAT macrophages, increases WAT mass, lowers energy expenditure, and exacerbates HFD-induced obesity in vivo. Collectively, this study suggests that adipocytes and macrophages employ intercellular mitochondria transfer as a mechanism of immunometabolic crosstalk that regulates metabolic homeostasis and is impaired in obesity.Entities:
Keywords: beige adipose tissue; brown adipose tissue; horizontal mitochondria transfer; immunometabolism; intercellular mitochondria transfer; macrophage; metabolism; mitochondria; obesity; white adipose tissue
Mesh：
Year: 2020 PMID： 33278339 PMCID： PMC7858234 DOI： 10.1016/j.cmet.2020.11.008
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287