The commitment of mesenchymal stem cells to preadipocytes is stimulated by hormonal induction. Preadipocytes induced to differentiate repress protein synthesis, remodel their cytoskeleton, and increase mitochondrial function to support anabolic pathways. These changes enable differentiation into mature adipocytes. Our understanding of the factors that coordinately regulate the early events of adipocyte differentiation remains incomplete. Here, by using multipronged approaches, we have identified zinc finger CCCH-type containing 10 (Zc3h10) as a critical regulator of the early stages of adipogenesis. Zc3h10 depletion in preadipocytes resulted in increased protein translation and impaired filamentous (F)-actin remodeling, with the latter detrimental effect leading to mitochondrial and metabolic dysfunction. These defects negatively affected differentiation to mature adipocytes. In contrast, Zc3h10 overexpression yielded mature adipocytes with remarkably increased lipid droplet size. Overall, our study establishes Zc3h10 as a fundamental proadipogenic transcription factor that represses protein synthesis and promotes F-actin/mitochondria dynamics to ensure proper energy metabolism and favor lipid accumulation.
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1 March 2021
Article|
February 10 2021
Zc3h10 regulates adipogenesis by controlling translation and F-actin/mitochondria interaction
Matteo Audano
,
1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
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Silvia Pedretti
,
1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
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Simona Ligorio
,
Simona Ligorio
1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
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Francesco Gualdrini
,
Francesco Gualdrini
2
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
3
Humanitas University (Hunimed), Pieve Emanuele, Milan, Italy
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Sara Polletti
,
Sara Polletti
2
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
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Marta Russo
,
Marta Russo
2
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
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Serena Ghisletti
,
Serena Ghisletti
2
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
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Camilla Bean
,
Camilla Bean
4
Department of Biology, University of Padova, Padua, Italy
5
Veneto Institute of Molecular Medicine, Padua, Italy
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Maurizio Crestani
,
Maurizio Crestani
1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
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Donatella Caruso
,
Donatella Caruso
1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
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Emma De Fabiani
,
1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
Correspondence to Emma De Fabiani: emma.defabiani@unimi.it
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Nico Mitro
1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
Nico Mitro: nico.mitro@unimi.it
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Matteo Audano
1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
Silvia Pedretti
1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
Simona Ligorio
1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
Francesco Gualdrini
2
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
3
Humanitas University (Hunimed), Pieve Emanuele, Milan, Italy
Sara Polletti
2
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
Marta Russo
2
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
Serena Ghisletti
2
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
Camilla Bean
4
Department of Biology, University of Padova, Padua, Italy
5
Veneto Institute of Molecular Medicine, Padua, Italy
Maurizio Crestani
1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
Donatella Caruso
1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
Emma De Fabiani
1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
Nico Mitro
1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
Correspondence to Emma De Fabiani: emma.defabiani@unimi.it
Nico Mitro: nico.mitro@unimi.it
*
M. Audano and S. Pedretti contributed equally to this paper.
Received:
April 27 2020
Revision Received:
October 29 2020
Accepted:
December 04 2020
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding:
European Foundation for the Study of Diabetes
(NO AWARD)
Fondazione Cariplo
(2014-0991)
Giovanni Armenise-Harvard Foundation
(NO AWARD)
Ministero dell’Istruzione, dell’Università e della Ricerca
(2018-2022)
© 2021 Audano et al.
2021
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2021) 220 (3): e202003173.
Article history
Received:
April 27 2020
Revision Received:
October 29 2020
Accepted:
December 04 2020
Citation
Matteo Audano, Silvia Pedretti, Simona Ligorio, Francesco Gualdrini, Sara Polletti, Marta Russo, Serena Ghisletti, Camilla Bean, Maurizio Crestani, Donatella Caruso, Emma De Fabiani, Nico Mitro; Zc3h10 regulates adipogenesis by controlling translation and F-actin/mitochondria interaction. J Cell Biol 1 March 2021; 220 (3): e202003173. doi: https://doi.org/10.1083/jcb.202003173
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