The role of mitochondrial fusion and StAR phosphorylation in the regulation of StAR activity and steroidogenesis

• StAR phosphorylation by ERK is a novel mechanism by which StAR is localized on the OMM.
• Mitochondrial fusion participates in StAR correct localization on the OMM.
• ERK-dependent StAR phosphorylation regulates mitochondrial cholesterol trafficking.

The steroidogenic acute regulatory (StAR) protein regulates the rate-limiting step in steroidogenesis, i.e. the delivery of cholesterol from the outer (OMM) to the inner (IMM) mitochondrial membrane. StAR is a 37-kDa protein with an N-terminal mitochondrial targeting sequence that is cleaved off during mitochondrial import to yield 30-kDa intramitochondrial StAR. StAR acts exclusively on the OMM and its activity is proportional to how long it remains on the OMM. However, the precise fashion and the molecular mechanism in which StAR remains on the OMM have not been elucidated yet. In this work we will discuss the role of mitochondrial fusion and StAR phosphorylation by the extracellular signal-regulated kinases 1/2 (ERK1/2) as part of the mechanism that regulates StAR retention on the OMM and activity.