The Causative Gene in Chanarian Dorfman Syndrome Regulates Lipid Droplet Homeostasis in C. elegans

Amp-activated kinase (ampk) is a key regulator of many cellular mechanisms required for adjustment to various stresses induced by the changing environment. in c. elegans dauer larvae ampk-null mutants expire prematurely due to hyperactive adipose triglyceride lipase (atgl-1) followed by rapid depletion of triglyceride stores. we found that the compromise of one of the three c. elegans orthologues of human cgi-58 significantly improves the survival of ampk-deficient dauers. we also provide evidence that c. elegans cgi-58 acts as a co-activator of atgl-1,while it also functions cooperatively to maintain regular lipid droplet structure. surprisingly,we show that it also acts independently of atgl-1 to restrict lipid droplet coalescence by altering the surface abundance and composition of long chain (c20) polyunsaturated fatty acids (pufas). our data reveal a novel structural role of cgi-58 in maintaining lipid droplet homeostasis through its effects on droplet composition,morphology and lipid hydrolysis; a conserved function that may account for some of the atgl-1-independent features unique to chanarin-dorfman syndrome. © 2015 xie,roy.