Turnover of StAR protein: Roles for the proteasome and mitochondrial proteases

Zvi Granot, Naomi Melamed-Book, Assaf Bahat, Joseph Orly*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

30 Scopus citations

Abstract

Steroidogenic acute regulatory protein (StAR) is a mitochondrial protein essential for massive synthesis of steroid hormones in the adrenal and the gonads. Our studies suggest that once synthesized on free polyribosomes, StAR preprotein either associates with the outer mitochondrial membrane to mediate transfer of cholesterol substrate required for steroidgenesis, or it is degraded by the proteasome. Proteasome inhibitors can prevent the turnover of StAR preprotein and other matrix-targeted preproteins. Once imported, excessive accumulation of inactive StAR in the matrix is avoided by a rapid turnover. Unexpectedly, mitochondrial StAR turnover can be inhibited by two proteasome inhibitors, i.e., MG132 and clasto-lactacystin β-lactone, but not epoxomicin. Use of those inhibitors and immuno-electron micoroscopy data enabled a clear distinction between two pools of intra-mitochondrial StAR, one degraded by matrix protease(s) shortly after import, while the rest of the protein undergoes a slower and inhibitor resistant degradation following translocation onto to the matrix face of the inner membranes.

Original languageAmerican English
Pages (from-to)51-58
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume265-266
Issue numberSUPPL.
DOIs
StatePublished - Feb 2007

Bibliographical note

Funding Information:
We thank Dr. Walter Miller, Dr. Bernard Schimmer and Dr. Paolo Bernardi for their inspiring comments discussing the presented observations, and Noa Sher for editorial help. This research was supported by the Israel Science Foundation grant 592/03.

Keywords

  • Mitochondrial proteases
  • Proteasome inhibitors
  • StAR turnover

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