The flat Golgi cisterna is a highly conserved feature of eukaryotic cells, but how is this morphology achieved and is it related to its function in cargo sorting and export? A physical model of cisterna morphology led us to propose that sphingomyelin (SM) metabolism at the trans-Golgi membranes in mammalian cells essentially controls the structural features of a Golgi cisterna by regulating its association to curvature-generating proteins. An experimental test of this hypothesis revealed that affecting SM homeostasis converted flat cisternae into highly curled membranes with a concomitant dissociation of membrane curvature-generating proteins. These data lend support to our hypothesis that SM metabolism controls the structural organization of a Golgi cisterna. Together with our previously presented role of SM in controlling the location of proteins involved in glycosylation and vesicle formation, our data reveal the significance of SM metabolism in the structural organization and function of Golgi cisternae.

FC and MGP acknowledge support by the Spanish Ministry of Economy and Competitiveness ('Severo Ochoa' Programme for Centres of Excellence in R and D (SEV-2015-240522) and FIS2014-56107-R), BFU2015-73288-JIN, AEI/FEDER;UE, Fundacion Privada Cellex, HFSP (GA RGP0027/2012), EC FP7-NANO-VISTA (GA 288263) and LaserLab 4 Europe (GA 654148). MMK is supported by the Israel Science Foundation. VM acknowledges support from the Spanish Ministry of Economy and Competitiveness through the Programme 'Centro de Excelencia Severo Ochoa 2013-298 2017' (SEV-2012-0208); and support from the CERCA Programme / Generalitat de Catalunya. VM is an Institucio´ Catalana de Recerca i Estudis Avanc¸ ats (ICREA) professor at the Center for Genomic Regulation and the work in his laboratory is funded by grants from MINECO's Plan Nacional (BFU2013-44188-P), Consolider (CSD2009-00016), and European Research Council (268692). The project has received research funding from the European Union.