Next Article in Journal
Molecular Mechanisms and Translational Therapies for Human Epidermal Receptor 2 Positive Breast Cancer
Next Article in Special Issue
Classical and Novel TSPO Ligands for the Mitochondrial TSPO Can Modulate Nuclear Gene Expression: Implications for Mitochondrial Retrograde Signaling
Previous Article in Journal
Regulation of Ketone Body Metabolism and the Role of PPARα
Previous Article in Special Issue
Regulation of Translocator Protein 18 kDa (TSPO) Expression in Rat and Human Male Germ Cells
Article Menu
Issue 12 (December) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(12), 2096; doi:10.3390/ijms17122096

Effect of the CRAC Peptide, VLNYYVW, on mPTP Opening in Rat Brain and Liver Mitochondria

1
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya Str., Pushchino, Moscow Region 142290, Russia
2
Departments of Drug Discovery & Biomedical Sciences and Biochemistry & Molecular Biology, Medical University of South Carolina, DD504 Drug Discovery Bldg., 70 President St., MSC 140, Charleston, SC 29425, USA
3
The Research Institute of the McGill University Health Center, and Departments of Medicine, Biochemistry, Pharmacology and Therapeutics, McGill University, 2155 Guy Street, Montreal, QC H3H 2R9, Canada
*
Author to whom correspondence should be addressed.
Academic Editors: Giovanni Natile and Nunzio Denora
Received: 25 September 2016 / Revised: 1 December 2016 / Accepted: 7 December 2016 / Published: 13 December 2016
(This article belongs to the Special Issue Translocator Protein (TSPO))
View Full-Text   |   Download PDF [2194 KB, uploaded 13 December 2016]   |  

Abstract

The translocator protein (TSPO; 18 kDa) is a high-affinity cholesterol-binding protein located in the outer membrane of mitochondria. A domain in the C-terminus of TSPO was characterized as the cholesterol recognition/interaction amino acid consensus (CRAC). The ability of the CRAC domain to bind to cholesterol led us to hypothesize that this peptide may participate in the regulation of mitochondrial membrane permeability. Herein, we report the effect of the synthetic CRAC peptide, VLNYYVW, on mitochondrial permeability transition pore (mPTP) opening. It was found that the CRAC peptide alone prevents the mPTP from opening, as well as the release of apoptotic factors (cytochrome c, AIF, and EndoG) in rat brain mitochondria (RBM). Co-incubation of CRAC, together with the TSPO drug ligand, PK 11195, resulted in the acceleration of mPTP opening and in the increase of apoptotic factor release. VLNYYVW did not induce swelling in rat liver mitochondria (RLM). 3,17,19-androsten-5-triol (19-Atriol; an inhibitor of the cholesterol-binding activity of the CRAC peptide) alone and in combination with the peptide was able to stimulate RLM swelling, which was Ca2+- and CsA-sensitive. Additionally, a combination of 19-Atriol with 100 nM PK 11195 or with 100 µM PK 11195 displayed the opposite effect: namely, the addition of 19-Atriol with 100 µM PK 11195 in a suspension of RLM suppressed the Ca2+-induced swelling of RLM by 40%, while the presence of 100 nM PK 11195 with 19-Atriol enhanced the swelling of RLM by 60%. Taken together, these data suggest the participation of the TSPO’s CRAC domain in the regulation of permeability transition. View Full-Text
Keywords: mitochondria; translocator protein (TSPO); cholesterol recognition/interaction amino acid consensus (CRAC); permeability transition mitochondria; translocator protein (TSPO); cholesterol recognition/interaction amino acid consensus (CRAC); permeability transition
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Azarashvili, T.; Krestinina, O.; Baburina, Y.; Odinokova, I.; Akatov, V.; Beletsky, I.; Lemasters, J.; Papadopoulos, V. Effect of the CRAC Peptide, VLNYYVW, on mPTP Opening in Rat Brain and Liver Mitochondria. Int. J. Mol. Sci. 2016, 17, 2096.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top