THE RNA BINDING PROTEIN ZC3H10 COUPLES MITOCHONDRIAL FUNCTION AND IRON METABOLISM

Mitochondria play a crucial role in energy metabolism. Mitochondria have their own genome (mtDNA), whose replication and transcription are mainly regulated by the mitochondrial transcription factor A (Tfam). Recent researches demonstrate how mitochondria participate to a large number of cellular processes like cell cycle and differentiation. Our goal is to identify new mitochondrial regulators to light up the molecular mechanisms underlying mitochondrial function biology. We used a high throughput screening in 293 cells in order to identify positive mitochondrial regulators. By these means, we identified Zinc Finger CCCH-type containing 10 (Zc3h10) as the best hit. Following experiments demonstrated that Zc3h10 knockdown decreased mitochondrial function and differentiation in myotubes. RNA immunoprecipitation assay indicates that Zc3h10 is able to bind 410 transcripts. Several target genes are involved in energy metabolism and iron balance. Notably, Zc3h10 downregulation in C2C12 leads to iron overload while its overexpression restores ferric ion content to control levels. Collectively, our findings annotate Zc3h10 as a new mitochondrial regulator in skeletal muscle.