THE NOVEL MITOCHONDRIAL REGULATOR ZC3H10 CONTROLS THE WHITE ADIPOCYTE DIFFERENTIATION PROGRAM

Mitochondria play a crucial role in many cellular processes, and they are essential organelles for the cell’s health. Beside their contribution to energy production, they are key regulators of tissue development and cell differentiation. In this context, a new mitochondrial regulator, zinc finger CCCH-type containing 10 (Zc3h10) protein has been recently discovered, and we validated its role during white adipocytes differentiation. The commitment of mesenchymal stem cells to pre-adipocytes is stimulated by hormonal induction. During adipocytes differentiation, pre-adipocytes undergo blunted protein synthesis, cytoskeleton remodeling and increased mitochondrial function to support anabolic pathways. All these molecular changes enable differentiation into mature adipocytes. We found that Zc3h10 is a critical regulator of the early stages of adipogenesis. Indeed, Zc3h10 depletion in pre-adipocytes resulted in increased protein translation and impaired filamentous (F)-actin remodeling, thus resulting in mitochondrial and metabolic dysfunction, incorrect mitotic clonal expansion (MCE), impaired lipid accumulation and terminal differentiation. In contrast, Zc3h10 overexpression yielded mature adipocytes with remarkably increased lipid droplet size. Overall, our results establish Zc3h10 as a fundamental pro-adipogenic transcription factor that represses protein synthesis and promotes F-actin/mitochondria dynamics to ensure proper energy metabolism, MCE and favor lipid accumulation to allow final adipocytes differentiation.