Arabidopsis 3-hydroxy-3-methylglutaryl-CoA reductase is regulated at the post-translational level in response to alterations of the sphingolipid and the sterol biosynthetic pathways.

3-Hydroxy-3-methylglutaryl-CoA reductase (HMGR, EC 1.1.1.34) catalyzes the major rate-limiting step in the mevalonate (MVA) pathway for isoprenoid biosynthesis. Its activity is regulated at different levels, from transcriptional to post-translational. Treatment of Arabidopsis thaliana plants with myriocin, a specific inhibitor of serine palmitoyltransferase (SPT), the first enzyme of sphingolipid biosynthesis, resulted in a concomitant reduction of both HMGR activity and the sterol content, which reveals regulatory cross-talk between these two lipid biosynthesis pathways. Myriocin-induced down-regulation of HMGR activity is exerted at the post-translational level, like the regulatory response of HMGR to enhancement or depletion of the flux through the sterol pathway.