Reperfusion mediates heme impairment with increased protein cysteine sulfonation of mitochondrial complex III in the post-ischemic heart.

Title

Reperfusion mediates heme impairment with increased protein cysteine sulfonation of mitochondrial complex III in the post-ischemic heart.

Creator

Chen C; Kang PT; Zhang L; Xiao K; Zweier JL; Chilian WM; Chen Y-R

Publisher

Journal of Molecular and Cellular Cardiology

Date

2021
2021-07-28

Description

A serious consequence of myocardial ischemia-reperfusion injury (I/R) is oxidative damage, which causes mitochondrial dysfunction. The cascading ROS can propagate and potentially induce heme bleaching and protein cysteine sulfonation (PrSO 3 H) of the mitochondrial electron transport chain. Herein we studied the mechanism of I/R-mediated irreversible oxidative injury of complex III in mitochondria from rat hearts subjected to 30-min of ischemia and 24-h of reperfusion in vivo. In the I/R region, the catalytic activity of complex III was significantly impaired. Spectroscopic analysis indicated that I/R mediated the destruction of hemes b and c + c 1 in the mitochondria, supporting I/R-mediated complex III impairment. However, no significant impairment of complex III activity and heme damage were observed in mitochondria from the risk region of rat hearts subjected only to 30-min ischemia, despite a decreased state 3 respiration. In the I/R mitochondria, carbamidomethylated C 122 /C 125 of cytochrome c 1 via alkylating complex III with a down regulation of HCCS was exclusively detected, supporting I/R-mediated thioether defect of heme c 1 . LC-MS/MS analysis showed that I/R mitochondria had intensely increased complex III PrSO 3 H levels at the C 236 ligand of the [2Fe2S] cluster of the Rieske iron‑sulfur protein (uqcrfs1), thus impairing the electron transport activity. MS analysis also indicated increased PrSO 3 H of the hinge protein at C 65 and of cytochrome c 1 at C 140 and C 220 , which are confined in the intermembrane space. MS analysis also showed that I/R extensively enhanced the PrSO 3 H of the core 1 (uqcrc1) and core 2 (uqcrc2) subunits in the matrix compartment, thus supporting the conclusion that complex III releases ROS to both sides of the inner membrane during reperfusion. Analysis of ischemic mitochondria indicated a modest reduction from the basal level of complex III PrSO 3 H detected in the mitochondria of sham control hearts, suggesting that the physiologic hyperoxygenation and ROS overproduction during reperfusion mediated the enhancement of complex III PrSO 3 H. In conclusion, reperfusion-mediated heme damage with increased PrSO 3 H controls oxidative injury to complex III and aggravates mitochondrial dysfunction in the post-ischemic heart. (Copyright © 2018. Published by Elsevier Ltd.)

Subject

Complex III; Cysteine sulfonation; Heme damage; Myocardial ischemia and reperfusion; Oxidative stress; Protein structure

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Format

journalArticle

Search for Full-text

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ISSN

1095-8584

NEOMED College

NEOMED College of Medicine

NEOMED Department

Department of Integrative Medical Sciences

Update Year & Number

August 2021 List

Citation

Chen C; Kang PT; Zhang L; Xiao K; Zweier JL; Chilian WM; Chen Y-R, “Reperfusion mediates heme impairment with increased protein cysteine sulfonation of mitochondrial complex III in the post-ischemic heart.,” NEOMED Bibliography Database, accessed October 26, 2021, https://neomed.omeka.net/items/show/11765.

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