Cytosolic functions of MORC2 in lipogenesis and adipogenesis

Microrchidia (MORC) family CW-type zinc finger 2 (MORC2) has been shown to be involved in several nuclear processes, including transcription modulation and DNA damage repair. However, its cytosolic function remains largely unknown. Here, we report an interaction between MORC2 and adenosine triphosphate (ATP)-citrate lyase (ACLY), an Enzyme that catalyzes the formation of acetyl-coA and plays a central role in lipogenesis, cholesterogenesis, and histone acetylation. Furthermore, we demonstrate that MORC2 promotes ACLY activation in the cytosol of lipogenic breast Cancer cells and plays an essential role in lipogenesis, adipogenesis and differentiation of 3T3-L1 preadipocytic cells. Consistently, the expression of MORC2 is induced during the process of 3T3-L1 adipogenic differentiation and mouse mammary gland development at a stage of increased lipogenesis. This observation was accompanied by a high ACLY activity. Together, these results demonstrate a cytosolic function of MORC2 in lipogenesis, adipogenic differentiation, and lipid homeostasis by regulating the activity of ACLY.

3-hydroxyl-3-methylglutaryl-coA reductase; 3-isobutyl-1-methylxanthine; ACC; ACLY; ATP; ATP citrate lyase; Adipogenesis; FAS; GSK-3; GST; HMGCR; IBMX; IP; Lipogenesis; MDH; MORC2; Microrchidia family CW-type zinc finger 2; PKA; Protein–protein interaction; RIPA; ZF; acetyl-coA carboxylase; adenosine triphosphate; cAMP-dependent protein kinase; fatty acid synthase; glutathione-S-transferase; glycogen synthase kinase-3; immunoprecipitation; malate dehydrogenase; radio-immunoprecipitation assay; zinc finger.