Mg2+ Extrusion from Intestinal Epithelia by CNNM Proteins Is Essential for Gonadogenesis via AMPK-TORC1 Signaling in Caenorhabditis elegans

Mg2+ serves as an essential cofactor for numerous enzymes and its levels are tightly regulated by various mg2+ transporters. here,we analyzed caenorhabditis elegans strains carrying mutations in genes encoding cyclin m (cnnm) mg2+ transporters. we isolated inactivating mutants for each of the five caenorhabditis elegans cnnm family genes,cnnm-1 through cnnm-5. cnnm-1; cnnm-3 double mutant worms showed various phenotypes,among which the sterile phenotype was rescued by supplementing the media with mg2+. this sterility was caused by a gonadogenesis defect with severely attenuated proliferation of germ cells. using this gonadogenesis defect as an indicator,we performed genome-wide rnai screening,to search for genes associated with this phenotype. the results revealed that rnai-mediated inactivation of several genes restores gonad elongation,including aak-2,which encodes the catalytic subunit of amp-activated protein kinase (ampk). we then generated triple mutant worms for cnnm-1; cnnm-3; aak-2 and confirmed that the aak-2 mutation also suppressed the defective gonadal elongation in cnnm-1; cnnm-3 mutant worms. ampk is activated under low-energy conditions and plays a central role in regulating cellular metabolism to adapt to the energy status of cells. thus,we provide genetic evidence linking mg2+ homeostasis to energy metabolism via ampk. © 2016 ishii et al.