Cysteine 202 of cyclophilin D is a site of multiple post-translational modifications and plays a role in cardioprotection.

Cardiovascular Research
Georgios AmanakisElizabeth Murphy

Abstract

Cyclophilin-D is a well-known regulator of the mitochondrial permeability transition pore (PTP), the main effector of cardiac ischaemia/reperfusion injury. However, the binding of CypD to the PTP is poorly understood. Cysteine 202 (C202) of CypD is highly conserved among species and can undergo redox-sensitive post-translational modifications. We investigated whether C202 regulates the opening of PTP. We developed a knock-in mouse model using CRISPR where CypD-C202 was mutated to a serine (C202S). Infarct size is reduced in CypD-C202S Langendorff perfused hearts compared to wild type (WT). Cardiac mitochondria from CypD-C202S mice also have higher calcium retention capacity compared to WT. Therefore, we hypothesized that oxidation of C202 might target CypD to the PTP. Indeed, isolated cardiac mitochondria subjected to oxidative stress exhibit less binding of CypD-C202S to the proposed PTP component F1F0-ATP-synthase. We previously found C202 to be S-nitrosylated in ischaemic preconditioning. Cysteine residues can also undergo S-acylation, and C202 matched an S-acylation motif. S-acylation of CypD-C202 was assessed using a resin-assisted capture (Acyl-RAC). WT hearts are abundantly S-acylated on CypD C202 under baseline conditio...Continue Reading

References

Apr 1, 1995·The Biochemical Journal·E J Griffiths, A P Halestrap
Mar 15, 1996·The Journal of Biological Chemistry·P W ShaulT Michel
Apr 1, 1996·Journal of Bioenergetics and Biomembranes·P Bernardi, V Petronilli
Jun 20, 1997·The Journal of Biological Chemistry·J B MichelT Michel
Jun 1, 1997·Bioscience Reports·B V Chernyak
Mar 29, 2000·Biochemical and Biophysical Research Communications·K ScholichT B Patel
Jul 19, 2005·Molecular and Cellular Biology·Sandrine RoyJohn F Hancock
Sep 2, 2006·The International Journal of Biochemistry & Cell Biology·Jianqiang NiYouguo Huang
May 22, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Christopher P Baines
Mar 7, 2009·Journal of Molecular and Cellular Cardiology·Andrew P Halestrap
Sep 9, 2009·Archives of Biochemistry and Biophysics·Dominique LinardBernard Knoops
Oct 6, 2009·The Journal of Biological Chemistry·Valentina GiorgioGiovanna Lippe
Nov 4, 2010·Journal of Lipid Research·Michael T ForresterPatrick J Casey
Sep 21, 2011·The Journal of Biological Chemistry·Tiffany T NguyenElizabeth Murphy
Apr 14, 2012·Cardiovascular Research·David Garcia-DoradoHans Michael Piper
Feb 11, 2014·The Journal of Biological Chemistry·Ruchi ChaubeJonathan S Stamler
Jan 1, 2016·Proceedings of the National Academy of Sciences of the United States of America·Sabrina M HollandGareth M Thomas
Jul 7, 2017·Scientific Reports·Mark O CollinsJyoti S Choudhary
Jul 18, 2019·Molecular & Cellular Proteomics : MCP·Monika Zareba-KoziolJakub Wlodarczyk
Oct 1, 2019·Molecular & Cellular Proteomics : MCP·Monika Zareba-KoziolJakub Wlodarczyk

❮ Previous
Next ❯

Citations

Jul 7, 2020·Frontiers in Physiology·Georgios Amanakis, Elizabeth Murphy
Dec 23, 2020·Antioxidants·Wenjun Wang, Peter M Kang
Jul 25, 2021·International Journal of Molecular Sciences·Ang LiJingsong Zhou
Aug 17, 2021·American Journal of Physiology. Renal Physiology·Hee-Seong JangBabu J Padanilam
Oct 29, 2021·The FEBS Journal·Paolo BernardiGiovanna Lippe

❮ Previous
Next ❯

Related Concepts

Related Feeds

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

Related Papers

Journal of Bioenergetics and Biomembranes
Michael A Forte, Paolo Bernardi
Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Salvatore AntonucciElizabeth Murphy
© 2021 Meta ULC. All rights reserved