Tunicamycin-Induced Endoplasmic Reticulum Stress Damages Complex I in Cardiac Mitochondria
Background: Induction of acute ER (endoplasmic reticulum) stress using thapsigargin contributes to complex I damage in mouse hearts. Thapsigargin impairs complex I by increasing mitochondrial calcium through inhibition of Ca<sup>2+</sup>-ATPase in the ER. Tunicamycin (TUNI) is used to in...
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MDPI AG
2022-08-01
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Online Access: | https://www.mdpi.com/2075-1729/12/8/1209 |
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author | Qun Chen Jeremy Thompson Ying Hu Edward J. Lesnefsky |
author_facet | Qun Chen Jeremy Thompson Ying Hu Edward J. Lesnefsky |
author_sort | Qun Chen |
collection | DOAJ |
description | Background: Induction of acute ER (endoplasmic reticulum) stress using thapsigargin contributes to complex I damage in mouse hearts. Thapsigargin impairs complex I by increasing mitochondrial calcium through inhibition of Ca<sup>2+</sup>-ATPase in the ER. Tunicamycin (TUNI) is used to induce ER stress by inhibiting protein folding. We asked if TUNI-induced ER stress led to complex I damage. Methods: TUNI (0.4 mg/kg) was used to induce ER stress in C57BL/6 mice. Cardiac mitochondria were isolated after 24 or 72 h following TUNI treatment for mitochondrial functional analysis. Results: ER stress was only increased in mice following 72 h of TUNI treatment. TUNI treatment decreased oxidative phosphorylation with complex I substrates compared to vehicle with a decrease in complex I activity. The contents of complex I subunits including NBUPL and NDUFS7 were decreased in TUNI-treated mice. TUNI treatment activated both cytosolic and mitochondrial calpain 1. Our results indicate that TUNI-induced ER stress damages complex I through degradation of its subunits including NDUFS7. Conclusion: Induction of the ER stress using TUNI contributes to complex I damage by activating calpain 1. |
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spelling | doaj.art-2d93a3f2648848d98954740243b8f8bb2023-11-30T21:49:29ZengMDPI AGLife2075-17292022-08-01128120910.3390/life12081209Tunicamycin-Induced Endoplasmic Reticulum Stress Damages Complex I in Cardiac MitochondriaQun Chen0Jeremy Thompson1Ying Hu2Edward J. Lesnefsky3Division of Cardiology, Department of Medicine, Pauley Heart Center, Richmond, VA 23298, USADivision of Cardiology, Department of Medicine, Pauley Heart Center, Richmond, VA 23298, USADivision of Cardiology, Department of Medicine, Pauley Heart Center, Richmond, VA 23298, USADivision of Cardiology, Department of Medicine, Pauley Heart Center, Richmond, VA 23298, USABackground: Induction of acute ER (endoplasmic reticulum) stress using thapsigargin contributes to complex I damage in mouse hearts. Thapsigargin impairs complex I by increasing mitochondrial calcium through inhibition of Ca<sup>2+</sup>-ATPase in the ER. Tunicamycin (TUNI) is used to induce ER stress by inhibiting protein folding. We asked if TUNI-induced ER stress led to complex I damage. Methods: TUNI (0.4 mg/kg) was used to induce ER stress in C57BL/6 mice. Cardiac mitochondria were isolated after 24 or 72 h following TUNI treatment for mitochondrial functional analysis. Results: ER stress was only increased in mice following 72 h of TUNI treatment. TUNI treatment decreased oxidative phosphorylation with complex I substrates compared to vehicle with a decrease in complex I activity. The contents of complex I subunits including NBUPL and NDUFS7 were decreased in TUNI-treated mice. TUNI treatment activated both cytosolic and mitochondrial calpain 1. Our results indicate that TUNI-induced ER stress damages complex I through degradation of its subunits including NDUFS7. Conclusion: Induction of the ER stress using TUNI contributes to complex I damage by activating calpain 1.https://www.mdpi.com/2075-1729/12/8/1209calpainoxidative phosphorylationNDUFS7NBUPL |
spellingShingle | Qun Chen Jeremy Thompson Ying Hu Edward J. Lesnefsky Tunicamycin-Induced Endoplasmic Reticulum Stress Damages Complex I in Cardiac Mitochondria Life calpain oxidative phosphorylation NDUFS7 NBUPL |
title | Tunicamycin-Induced Endoplasmic Reticulum Stress Damages Complex I in Cardiac Mitochondria |
title_full | Tunicamycin-Induced Endoplasmic Reticulum Stress Damages Complex I in Cardiac Mitochondria |
title_fullStr | Tunicamycin-Induced Endoplasmic Reticulum Stress Damages Complex I in Cardiac Mitochondria |
title_full_unstemmed | Tunicamycin-Induced Endoplasmic Reticulum Stress Damages Complex I in Cardiac Mitochondria |
title_short | Tunicamycin-Induced Endoplasmic Reticulum Stress Damages Complex I in Cardiac Mitochondria |
title_sort | tunicamycin induced endoplasmic reticulum stress damages complex i in cardiac mitochondria |
topic | calpain oxidative phosphorylation NDUFS7 NBUPL |
url | https://www.mdpi.com/2075-1729/12/8/1209 |
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