Reactome | STAR mediates CHOL translocation from cytosol to mitochondrial intermembrane space

STAR mediates CHOL translocation from cytosol to mitochondrial intermembrane space

Stable Identifier

R-HSA-196126

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial outer membrane, cytosol, mitochondrial intermembrane space

Synonyms

cholesterol(in) = cholesterol(out)

ReviewStatus

5/5

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STAR mediates CHOL translocation from cytosol to mitochondrial intermembrane space

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CHOL (cholesterol) traverses the cytosol and the mitochondrial intermembrane space complexed with STARD cholesterol-binding proteins. A plausible model, supported by studies in vitro and in cells overexpressing cloned human proteins, is that cytosolic STARD proteins bind cholesterol liberated from lysosomes or cytosolic lipid droplets and carry it to the outer mitochondrial membrane (Rodriguez-Aguado et al. 2005; Soccio et al. 2002), where STAR steroidogenic acute regulatory protein mediates its delivery to the mitochondrial inner membrane (Miller 2007, Letourneau et al. 2015).

This process is essential for steroid hormone synthesis. Mutations in the gene encoding STAR block synthesis of all steroid hormones in humans (Bose et al. 1996). The transport step is also a key site for normal regulation of steroid hormone synthesis, as STAR protein is unstable and its synthesis is up-regulated in response to signals such as the binding of ACTH to its receptors on adrenal cells (Stocco 2001).

Literature References

PubMed ID	Title	Journal	Year
25542846	The binding site specificity of STARD4 subfamily: Breaking the cholesterol paradigm Létourneau, D, Lefebvre, A, Lavigne, P, LeHoux, JG	Mol. Cell. Endocrinol.	2015