An Indispensable Role for Dynamin-related Protein 1 in Beige and Brown Adipogenesis

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2020 Aug 27

PMID 32843579

Citations 5

Authors

Raja Gopal Reddy Mooli

Dhanunjay Mukhi

Zhonghe Chen

Nia Buckner

Sadeesh K Ramakrishnan

Affiliations

Soon will be listed here.

Abstract

Emerging evidence indicates that proper mitochondrial dynamics are critical for adipocyte differentiation and functional thermogenic capacity. We found that the mitochondrial fission protein dynamin-related protein 1 (DRP1, also known as DNML1) is highly expressed in brown adipose tissue compared to expression in white adipose tissue, and these expression levels increase during brown adipocyte differentiation. Our results reveal that the inhibition of DRP1 using mdivi-1 mitigates beige adipocyte differentiation and differentiation-associated mitochondrial biogenesis. We found that DRP1 is essential for the induction of the early-phase beige adipogenic transcriptional program. Intriguingly, inhibition of DRP1 is dispensable following the induction of beige adipogenesis and adipogenesis-associated mitochondrial biogenesis. Altogether, we demonstrate that DRP1 in preadipocytes plays an essential role in beige and brown adipogenesis.This article has an associated First Person interview with the first author of the paper.

Citing Articles

Mitochondrial fission is required for thermogenesis in brown adipose tissue.

Ibayashi Y, Hasuzawa N, Nomura S, Kabashima M, Nagayama A, Iwata S PLoS One. 2024; 19(12):e0312352.

PMID: 39652536 PMC: 11627380. DOI: 10.1371/journal.pone.0312352.

Epigenetically active chromatin in neonatal iWAT reveals GABPα as a potential regulator of beige adipogenesis.

Mooli R, Zhu B, Khan S, Nagati V, Michealraj K, Jurczak M Front Endocrinol (Lausanne). 2024; 15:1385811.

PMID: 38765953 PMC: 11099907. DOI: 10.3389/fendo.2024.1385811.

Identification of crucial modules and genes associated with backfat tissue development by WGCNA in Ningxiang pigs.

Chen C, Ren H, Li H, Deng Y, Cui Q, Zhu J Front Genet. 2023; 14:1234757.

PMID: 37662841 PMC: 10469685. DOI: 10.3389/fgene.2023.1234757.

Regulation of Adipose Thermogenesis and its Critical Role in Glucose and Lipid Metabolism.

Wang L, Qiu Y, Gu H, Gan M, Zhu Y, Zhu K Int J Biol Sci. 2022; 18(13):4950-4962.

PMID: 35982903 PMC: 9379406. DOI: 10.7150/ijbs.75488.

Epigenetics, 1-Carbon Metabolism, and Homocysteine During Dysbiosis.

Singh M, Hardin S, George A, Eyob W, Stanisic D, Pushpakumar S Front Physiol. 2021; 11:617953.

PMID: 33708132 PMC: 7940193. DOI: 10.3389/fphys.2020.617953.

References

Cassidy-Stone A, Chipuk J, Ingerman E, Song C, Yoo C, Kuwana T . Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev Cell. 2008; 14(2):193-204. PMC: 2267902. DOI: 10.1016/j.devcel.2007.11.019. View

Dai W, Jiang L . Dysregulated Mitochondrial Dynamics and Metabolism in Obesity, Diabetes, and Cancer. Front Endocrinol (Lausanne). 2019; 10:570. PMC: 6734166. DOI: 10.3389/fendo.2019.00570. View

Feve B . Adipogenesis: cellular and molecular aspects. Best Pract Res Clin Endocrinol Metab. 2005; 19(4):483-99. DOI: 10.1016/j.beem.2005.07.007. View

Farmer S . Transcriptional control of adipocyte formation. Cell Metab. 2006; 4(4):263-73. PMC: 1958996. DOI: 10.1016/j.cmet.2006.07.001. View

Forni M, Peloggia J, Trudeau K, Shirihai O, Kowaltowski A . Murine Mesenchymal Stem Cell Commitment to Differentiation Is Regulated by Mitochondrial Dynamics. Stem Cells. 2015; 34(3):743-55. PMC: 4803524. DOI: 10.1002/stem.2248. View

Lu X, Altshuler-Keylin S, Wang Q, Chen Y, Sponton C, Ikeda K . Mitophagy controls beige adipocyte maintenance through a Parkin-dependent and UCP1-independent mechanism. Sci Signal. 2018; 11(527). PMC: 6410368. DOI: 10.1126/scisignal.aap8526. View

Chen H, Chan D . Mitochondrial Dynamics in Regulating the Unique Phenotypes of Cancer and Stem Cells. Cell Metab. 2017; 26(1):39-48. PMC: 5539982. DOI: 10.1016/j.cmet.2017.05.016. View

Kajimura S, Spiegelman B, Seale P . Brown and Beige Fat: Physiological Roles beyond Heat Generation. Cell Metab. 2015; 22(4):546-59. PMC: 4613812. DOI: 10.1016/j.cmet.2015.09.007. View

Seo B, Yoon S, Do J . Mitochondrial Dynamics in Stem Cells and Differentiation. Int J Mol Sci. 2018; 19(12). PMC: 6321186. DOI: 10.3390/ijms19123893. View

10.

Pisani D, Barquissau V, Chambard J, Beuzelin D, Ghandour R, Giroud M . Mitochondrial fission is associated with UCP1 activity in human brite/beige adipocytes. Mol Metab. 2017; 7:35-44. PMC: 5784321. DOI: 10.1016/j.molmet.2017.11.007. View

11.

Cannon B, Nedergaard J . Studies of thermogenesis and mitochondrial function in adipose tissues. Methods Mol Biol. 2008; 456:109-21. DOI: 10.1007/978-1-59745-245-8_8. View

12.

Vosselman M, van Marken Lichtenbelt W, Schrauwen P . Energy dissipation in brown adipose tissue: from mice to men. Mol Cell Endocrinol. 2013; 379(1-2):43-50. DOI: 10.1016/j.mce.2013.04.017. View

13.

Scott I, Youle R . Mitochondrial fission and fusion. Essays Biochem. 2010; 47:85-98. PMC: 4762097. DOI: 10.1042/bse0470085. View

14.

Kelly D, Scarpulla R . Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev. 2004; 18(4):357-68. DOI: 10.1101/gad.1177604. View

15.

Eisner V, Picard M, Hajnoczky G . Mitochondrial dynamics in adaptive and maladaptive cellular stress responses. Nat Cell Biol. 2018; 20(7):755-765. PMC: 6716149. DOI: 10.1038/s41556-018-0133-0. View

16.

Zhang Y, Chan D . New insights into mitochondrial fusion. FEBS Lett. 2007; 581(11):2168-73. PMC: 1941839. DOI: 10.1016/j.febslet.2007.01.095. View

17.

Mooli R, Mukhi D, Watt M, Edmunds L, Xie B, Capooci J . Sustained mitochondrial biogenesis is essential to maintain caloric restriction-induced beige adipocytes. Metabolism. 2020; 107:154225. PMC: 7284285. DOI: 10.1016/j.metabol.2020.154225. View

18.

Sidossis L, Kajimura S . Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis. J Clin Invest. 2015; 125(2):478-86. PMC: 4319444. DOI: 10.1172/JCI78362. View

19.

Wilson-Fritch L, Burkart A, Bell G, Mendelson K, Leszyk J, Nicoloro S . Mitochondrial biogenesis and remodeling during adipogenesis and in response to the insulin sensitizer rosiglitazone. Mol Cell Biol. 2003; 23(3):1085-94. PMC: 140688. DOI: 10.1128/MCB.23.3.1085-1094.2003. View

20.

Giralt M, Villarroya F . White, brown, beige/brite: different adipose cells for different functions?. Endocrinology. 2013; 154(9):2992-3000. DOI: 10.1210/en.2013-1403. View