StAR

ANA F. CASTILLO; ERNESTO J. PODESTÁ; PABLO G. MELE; CECILIA PODEROSO; PAULA MALOBERTI

Encyclopedia of Signaling Molecules, 2nd Edition

Springer International

Lugar: Nueva York; Año: 2018; p. 5161 - 5169

StAR is a unique protein that binds and transport cholesterol, from the outer to the inner mitochondrial membrane, participating in the rate-limiting step of the biosynthesis of all the steroids molecules, as well as bile salts in liver. StAR is undoubtedly a key regulatory protein in steroidogenesis, depicted by the fact that there is no other protein that could replace it or exert its function (with one exception in placenta). The structure of StAR is also quite particular since it presents a hydrophobic pocket fitting just one molecule of cholesterol. Nevertheless, StAR protein remains active as long as it is attached to the OMM probably transferring more than one cholesterol molecule per unit of StAR. StAR expression is subjected to numerous regulatory pathways, induced by trophic hormones in steroidogenic tissues, a great variety of transcription factors modulate StAR?s level in a positive or negative manner. Mitochondrial fusion exerts a transcriptional regulation through the presence of Mitofusin 2 by a yet unknown mechanism. One the most important and first described regulatory mechanism is phosphorylation of the protein. StAR is phosphorylated by PKA in two serine residues, being the serine nearest to the C-terminus completely necessary for StAR activity. Although this phospho-residue does not confers StAR complete activity since mutated StAR in this serine still remains some residual activity. This issue was later clarified when StAR was found to be substrate of ERK1/2, which directly phosphorylates StAR in mitochondria leading to StAR full activation along with PKA.The relevance of StAR activity is embodied by the fact that several and different mutation on its sequence provoke one of the most lethal endocrine pathology, lipoid CAH. But StAR presence and function is not just circumscribed to steroidogenic tissues but also to macrophages, skin, lung, adipose tissue, liver, endothelium, and diverse cancer cell lines, opening a wide spectrum of possibilities in StAR studies