Universität zu Köln

Bahat, Assaf, Perlberg, Shira, VIelamed-Book, Naomi, Isaac, Sara, Eden, Amir, Lauria, Ines ORCID: 0000-0001-5813-3103, Langer, Thomas ORCID: 0000-0003-1250-1462 and Orly, Joseph (2015). Transcriptional activation of LON Gene by a new form of mitochondrial stress: A role for the nuclear respiratory factor 2 in StAR overload response (SOR). Mol. Cell. Endocrinol., 408 (C). S. 62 - 73. CLARE: ELSEVIER IRELAND LTD. ISSN 0303-7207

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Abstract

High output of steroid hormone synthesis in steroidogenic cells of the adrenal cortex and the gonads requires the expression of the steroidogenic acute regulatory protein (StAR) that facilitates cholesterol mobilization to the mitochondrial inner membrane where the CYP11A1/P450scc enzyme complex converts the sterol to the first steroid. Earlier studies have shown that StAR is active while pausing on the cytosolic face of the outer mitochondrial membrane while subsequent import of the protein into the matrix terminates the cholesterol mobilization activity. Consequently, during repeated activity cycles, high level of post-active StAR accumulates in the mitochondrial matrix. To prevent functional damage due to such protein overload effect, StAR is degraded by a sequence of three to four ATP-dependent proteases of the mitochondria protein quality control system, including LON and the m-AAA membranous proteases AFG3L2 and SPG7/paraplegin. Furthermore, StAR expression in both peni-ovulatory ovarian cells, or under ectopic expression in cell line models, results in up to 3-fold enrichment of the mitochondrial proteases and their transcripts. We named this novel form of mitochondrial stress as StAR overload response (SOR). To better understand the SOR mechanism at the transcriptional level we analyzed first the unexplored properties of the proximal promoter of the LON gene. Our findings suggest that the human nuclear respiratory factor 2 (NRF-2), also known as GA binding protein (GABP), is responsible for 88% of the proximal promoter activity, including the observed increase of transcription in the presence of StAR. Further studies are expected to reveal if common transcriptional determinants coordinate the SOR induced transcription of all the genes encoding the SOR proteases. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bahat, Assaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Perlberg, Shira UNSPECIFIED UNSPECIFIED UNSPECIFIED VIelamed-Book, Naomi UNSPECIFIED UNSPECIFIED UNSPECIFIED Isaac, Sara UNSPECIFIED UNSPECIFIED UNSPECIFIED Eden, Amir 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:38-401082
DOI:	10.1016/j.mce.2015.02.022
Journal or Publication Title:	Mol. Cell. Endocrinol.
Volume:	408
Number:	C
Page Range:	S. 62 - 73
Date:	2015
Publisher:	ELSEVIER IRELAND LTD
Place of Publication:	CLARE
ISSN:	0303-7207
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACUTE REGULATORY PROTEIN; M-AAA PROTEASE; GA-BINDING-PROTEIN; OXIDATIVE STRESS; DOWN-REGULATION; PGC-1 FAMILY; DNA-BINDING; EXPRESSION; MECHANISM; AFG3L2 Multiple languages Cell Biology; Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40108