Zc3h10 regulates adipogenesis by controlling translation and F-actin/mitochondria interaction
Open Access
- 10 February 2021
- journal article
- research article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 220 (3)
- https://doi.org/10.1083/jcb.202003173
Abstract
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.Keywords
Funding Information
- Giovanni Armenise-Harvard Foundation
- CARIPLO foundation (2014-0991)
- European Foundation for the Study of Diabetes
- Lilly European Diabetes Research Program 2015
- MIUR Progetto Eccellenza
- MIUR (2018-2022)
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