StAR Recombinant Rabbit Monoclonal Antibody [JE32-23]

Function

The steroidogenic acute regulatory protein, commonly referred to as StAR (STARD1), is a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones. It is primarily present in steroid-producing cells, including theca cells and luteal cells in the ovary, Leydig cells in the testis and cell types in the adrenal cortex. Cholesterol needs to be transferred from the outer mitochondrial membrane to the inner membrane where cytochrome P450scc enzyme (CYP11A1) cleaves the cholesterol side chain, which is the first enzymatic step in all steroid synthesis. The aqueous phase between these two membranes cannot be crossed by the lipophilic cholesterol, unless certain proteins assist in this process. A number of proteins have historically been proposed to facilitate this transfer including: sterol carrier protein 2 (SCP2), steroidogenic activator polypeptide (SAP), peripheral benzodiazepine receptor (PBR or translocator protein, TSPO), and StAR. It is now clear that this process is primarily mediated by the action of StAR. The mechanism by which StAR causes cholesterol movement remains unclear as it appears to act from the outside of the mitochondria and its entry into the mitochondria ends its function. Various hypotheses have been advanced. Some involve StAR transferring cholesterol itself like a shuttle. While StAR may bind cholesterol itself, the exorbitant number of cholesterol molecules that the protein transfers would indicate that it would have to act as a cholesterol channel instead of a shuttle. Another notion is that it causes cholesterol to be kicked out of the outer membrane to the inner (cholesterol desorption). StAR may also promote the formation of contact sites between the outer and inner mitochondrial membranes to allow cholesterol influx. Another suggests that StAR acts in conjunction with PBR, causing the movement of Cl− out of the mitochondria to facilitate contact site formation. However, evidence for an interaction between StAR and PBR remains elusive.

Background References

1. Conde de la Rosa L et al. STARD1 promotes NASH-driven HCC by sustaining the generation of bile acids through the alternative mitochondrial pathway. J Hepatol. 2021 Jun

2. Larsen MC et al. STARD1 Functions in Mitochondrial Cholesterol Metabolism and Nascent HDL Formation. Gene Expression and Molecular mRNA Imaging Show Novel Splicing and a 1:1 Mitochondrial Association. Front Endocrinol (Lausanne). 2020 Oct

Subcellular Location

Mitochondrion.

UNIPROT

SwissProt: P49675 Human

Synonyms