HIGH STEROL ESTER 1 is a key factor in plant sterol homeostasis

Abstract

Plants strictly regulate the sterol levels in their cells, as high sterol levels are toxic. However, how plants achieve sterol homeostasis is not fully understood. We isolated anArabidopsis thaliana mutant that abundantly accumulated sterol esters in ~1-µmdiameter structures in leaf cells. We designated the mutant as high sterol ester 1 (hise1) and the structures as sterol ester (SE) bodies. Here we show that the gene product (HiSE1) responsible for the mutation functions as a key factor in plant sterol homeostasis on the endoplasmic reticulum (ER) and participates in a fail-safe-regulatory system composed of two processes. First, HiSE1 down-regulates the protein levels of the HMG-CoA reductases HMGR1 and HMGR2, which are rate-limiting enzymes in the sterol synthesis pathway, resulting in suppression of sterol overproduction. Second, if the first process is not successful, excess sterols are converted to sterol esters by phospholipid sterol acyltransferase1 (PSAT1) on the ER microdomains and then segregated in SE bodies.

Lipid composition and cell surface hydrophobicity of Candida albicans influence the efficacy of fluconazole–gentamicin treatment

“…The proper ratio of sterols to other lipids in PMs is necessary to maintain physiological structure and fluidity of the PM (Simons & Lkonen, 2000). In Eukaryota, the overproduction and elevated levels of sterols were reported to exhibit toxic effects towards the cells (Shimada et al, 2019;Tabas, 2002). In yeast cells, excessive ergosterol is either secreted into the extracellular environment or esterified and stored in lipid droplets (LDs) (Hu et al, 2017;Spanova et al, 2012).…”

Comparative Metabolomics Analysis Reveals Sterols and Sphingolipids Play a Role in Cotton Fiber Cell Initiation

“…GhHMGR1 was down-regulated in two mutant ovules maybe further suggest some sterol was overproduced. Consistently, the HMGR1 and HMGR2 were down-regulated in the high sterol ester 1 (hise1) mutant, in which abundantly accumulated sterol esters in leaf cells [ 67 ]. Therefore, the overproduction of campesterol and stigmasterol might be a key factor for the failure of fiber cell differentiation and initiation in the two mutants.…”

An update on the function and regulation of methylerythritol phosphate and mevalonate pathways and their evolutionary dynamics

“…Notably, while there are differences in membrane topology of HMGR from plants, yeasts, and mammals, HMGR protein levels in Medicago truncatula are also regulated by MAKIBISHI 1 (MKB1), an ER‐localized E3 ubiquitin ligase involved in ERAD (Pollier et al, 2013). Recently, an ER‐localized high sterol ester 1 (HISE1) was identified as a key player in Arabidopsis sterol homeostasis that negatively regulates the protein levels of HMGR (Shimada et al, 2019). The sequence similarity of HISE1 to a mammalian membrane protein suggests it controls ERAD‐mediated degradation of HMGR (Shimada et al, 2019).…”

“…Recently, an ER‐localized high sterol ester 1 (HISE1) was identified as a key player in Arabidopsis sterol homeostasis that negatively regulates the protein levels of HMGR (Shimada et al, 2019). The sequence similarity of HISE1 to a mammalian membrane protein suggests it controls ERAD‐mediated degradation of HMGR (Shimada et al, 2019). Together, these results indicate that a similar ERAD‐mediated degradation mechanism of HMGR exists in plants.…”