Universität zu Köln

Bahat, Assaf, Perlberg, Shira, Melamed-Book, Naomi, Lauria, Ines ORCID: 0000-0001-5813-3103, Langer, Thomas ORCID: 0000-0003-1250-1462 and Orly, Joseph (2014). StAR Enhances Transcription of Genes Encoding the Mitochondrial Proteases Involved in Its Own Degradation. Mol. Endocrinol., 28 (2). S. 208 - 225. CARY: OXFORD UNIV PRESS INC. ISSN 1944-9917

Full text not available from this repository.

Abstract

Steroidogenic acute regulatory protein (StAR) is essential for steroid hormone synthesis in the adrenal cortex and the gonads. StAR activity facilitates the supply of cholesterol substrate into the inner mitochondrial membranes where conversion of the sterol to a steroid is catalyzed. Mitochondrial import terminates the cholesterol mobilization activity of StAR and leads to mounting accumulation of StAR in the mitochondrial matrix. Our studies suggest that to prevent mitochondrial impairment, StAR proteolysis is executed by at least 2 mitochondrial proteases, ie, the matrix LON protease and the inner membrane complexes of the metalloproteases AFG3L2 and AFG3L2: SPG7/paraplegin. Gonadotropin administration to prepubertal rats stimulated ovarian follicular development associated with increased expression of the mitochondrial protein quality control system. In addition, enrichment of LON and AFG3L2 is evident in StAR-expressing ovarian cells examined by confocal microscopy. Furthermore, reporter studies of the protease promoters examined in the heterologous cell model suggest that StAR expression stimulates up to a 3.5-fold increase in the protease gene transcription. Such effects are StAR-specific, are independent of StAR activity, and failed to occur upon expression of StAR mutants that do not enter the matrix. Taken together, the results of this study suggest the presence of a novel regulatory loop, whereby acute accumulation of an apparent nuisance protein in the matrix provokes a mitochondria to nucleus signaling that, in turn, activates selected transcription of genes encoding the enrichment of mitochondrial proteases relevant for enhanced clearance of StAR.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bahat, Assaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Perlberg, Shira UNSPECIFIED UNSPECIFIED UNSPECIFIED Melamed-Book, Naomi UNSPECIFIED UNSPECIFIED UNSPECIFIED Lauria, Ines UNSPECIFIED orcid.org/0000-0001-5813-3103 UNSPECIFIED Langer, Thomas UNSPECIFIED orcid.org/0000-0003-1250-1462 UNSPECIFIED Orly, Joseph UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-447759
DOI:	10.1210/me.2013-1275
Journal or Publication Title:	Mol. Endocrinol.
Volume:	28
Number:	2
Page Range:	S. 208 - 225
Date:	2014
Publisher:	OXFORD UNIV PRESS INC
Place of Publication:	CARY
ISSN:	1944-9917
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACUTE REGULATORY PROTEIN; M-AAA PROTEASE; HEREDITARY SPASTIC PARAPLEGIA; SIDE-CHAIN CLEAVAGE; LIPOID ADRENAL-HYPERPLASIA; CELL-SPECIFIC EXPRESSION; ELEMENT-BINDING-PROTEIN; LON PROTEASE; FOLLICULAR DEVELOPMENT; STEROIDOGENIC ACTIVITY Multiple languages Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44775