Research ArticleCELL BIOLOGY

Mitochondrial metabolic regulation by GRP78

See allHide authors and affiliations

Science Advances  24 Feb 2017:
Vol. 3, no. 2, e1602038
DOI: 10.1126/sciadv.1602038

You are currently viewing the abstract.

View Full Text


Steroids, essential for mammalian survival, are initiated by cholesterol transport by steroidogenic acute regulatory protein (StAR). Appropriate protein folding is an essential requirement of activity. Endoplasmic reticulum (ER) chaperones assist in folding of cytoplasmic proteins, whereas mitochondrial chaperones fold only mitochondrial proteins. We show that glucose regulatory protein 78 (GRP78), a master ER chaperone, is also present at the mitochondria-associated ER membrane (MAM), where it folds StAR for delivery to the outer mitochondrial membrane. StAR expression and activity are drastically reduced following GRP78 knockdown. StAR folding starts at the MAM region; thus, its cholesterol fostering capacity is regulated by GRP78 long before StAR reaches the mitochondria. In summary, GRP78 is an acute regulator of steroidogenesis at the MAM, regulating the intermediate folding of StAR that is crucial for its activity.

  • mitochondria
  • Steroids
  • StAR
  • GRP78
  • mitochondria-associated ER membrane
  • mitochondrial chaperones

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

View Full Text