NDLI: The mitochondrial environment is required for activity of the cholesterol side-chain cleavage enzyme, cytochrome P450scc.

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The mitochondrial environment is required for activity of the cholesterol side-chain cleavage enzyme, cytochrome P450scc.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Harikrishna, J. A. Miller, W. L. Szklarz, G. D. Black, S. M.
Description	Author Affiliation: Black SM ( Department of Pediatrics, University of California, San Francisco 94143-0978.);
Abstract	Steroidogenesis is initiated by the conversion of cholesterol to pregnenolone by mitochondrial cytochrome P450scc [cholesterol, reduced-adrenal-ferredoxin:oxygen oxidoreductase (side-chain-cleaving); EC 1.14.15.6]. Several subsequent steroidal conversions occur in the endoplasmic reticulum (ER), but the last step in the production of glucocorticoids and mineralocorticoids again occurs in the mitochondria. Although cellular compartmentalization of steroidogenic enzymes appears to be a feature of all steroidogenic pathways, some reports indicate that cholesterol can be converted to pregnenolone outside the mitochondria. To investigate whether P450scc can function outside the mitochondria, we constructed vectors producing P450scc and various fusion enzymes of P450scc with electron-transport proteins and directed their expression to either the ER or the mitochondria. Whether targeted to mitochondria or to the ER, plasmid vectors encoding P450scc and fusion proteins of P450scc with either mitochondrial or microsomal electron-transport proteins produced immunodetectable protein. When expressed in mitochondria, all of these constructions converted 22-hydroxycholesterol to pregnenolone, but when expressed in the ER none of them produced pregnenolone. These results show that P450scc can function only in the mitochondria. Furthermore, it appears to be the mitochondrial environment that is required, rather than the specific mitochondrial electron-transport intermediates.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	15
Volume Number	91
Language	English
Publisher	National Academy of Sciences
Publisher Date	1994-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cholesterol Side-Chain Cleavage Enzyme Metabolism Cholesterol Mitochondria Enzymology Animals Cell Line Genetics Cloning, Molecular DNA Electron Transport Endoplasmic Reticulum Molecular Sequence Data Pregnenolone Protein Sorting Signals Recombinant Fusion Proteins Biosynthesis Transcription, Genetic Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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