Chen Qun, Thompson Jeremy, Hu Ying, Lesnefsky Edward J
Division of Cardiology, Department of Medicine, Pauley Heart Center, Richmond, VA 23298, USA.
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Life (Basel). 2022 Aug 9;12(8):1209. doi: 10.3390/life12081209.
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-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.
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.
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.
Induction of the ER stress using TUNI contributes to complex I damage by activating calpain 1.
使用毒胡萝卜素诱导急性内质网（ER）应激会导致小鼠心脏复合体I损伤。毒胡萝卜素通过抑制内质网中的钙 - ATP酶增加线粒体钙含量，从而损害复合体I。衣霉素（TUNI）用于通过抑制蛋白质折叠来诱导内质网应激。我们探究了衣霉素诱导的内质网应激是否会导致复合体I损伤。
使用衣霉素（0.4mg/kg）诱导C57BL/6小鼠的内质网应激。在衣霉素处理24或72小时后分离心脏线粒体，用于线粒体功能分析。
仅在衣霉素处理72小时后的小鼠中内质网应激增加。与载体相比，衣霉素处理降低了复合体I底物的氧化磷酸化，同时复合体I活性降低。衣霉素处理的小鼠中包括NBUPL和NDUFS7在内的复合体I亚基含量降低。衣霉素处理激活了胞质和线粒体钙蛋白酶1。我们的结果表明，衣霉素诱导的内质网应激通过降解包括NDUFS7在内的亚基来损害复合体I。
使用衣霉素诱导内质网应激通过激活钙蛋白酶1导致复合体I损伤。
