Regulation of brefeldin A-induced ER stress and apoptosis by mitochondrial NADP+-dependent isocitrate dehydrogenase

Moon, Jung Lee; Kim, Sung Youl; Shin, Seoungwoo; Park, Jeen‐Woo

doi:10.1016/j.bbrc.2011.12.030

Cited by 54 publications

(30 citation statements)

References 24 publications

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“…IDH2 can be inactivated by peroxynitrite, as shown recently by alcohol feeding resulting in decreased NADPH equivalents and subsequent GSH defense [49]. In line with these observations, it has been reported that IDH2 silencing sensitizes tumor cells to apoptosis in response to various stimuli, including brefeldin A, anticancer drugs, tumor necrosis factor-α, doxorubicin, actinomycin D and etoposide [50, 51]. Whether this outcome is related directly to perturbation of NADPH equivalents or to the generation of oncometabolites such (R)-2-hydroxyglutarate and subsequent alterations in hypoxia signaling and DNA methylation remains to be established [52].…”

Section: Introductionmentioning

confidence: 75%

Mitochondrial glutathione: Features, regulation and role in disease

Marı́

Morales

Colell

et al. 2013

Biochimica et Biophysica Acta (BBA) - General Subjects

173

117

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BACKGROUND Mitochondria are the powerhouse of mammalian cells and the main source of reactive oxygen species (ROS) associated with oxygen consumption. In addition, they also play a strategic role in controlling the fate of cells through regulation of death pathways. Mitochondrial ROS production fulfills a signaling role through regulation of redox pathways, but also contributes to mitochondrial damage in a number of pathological states. SCOPE OF REVIEW Mitochondria are exposed to the constant generation of oxidant species, and yet the organelle remains functional due to the existence of an armamentarium of antioxidant defense systems aimed to repair oxidative damage, of which mitochondrial glutathione (mGSH) is of particular relevance. Thus, the aim of the review is to cover the regulation of mGSH and its role in disease. MAJOR CONCLUSIONS Cumulating evidence over recent years has demonstrated the essential role for mGSH in mitochondrial physiology and disease. Despite its high concentration in the mitochondrial matrix, mitochondria lack the enzymes to synthesize GSH de novo, so that mGSH originates from cytosolic GSH via transport through specific mitochondrial carriers, which exhibit sensitivity to membrane dynamics. Depletion of mGSH sensitizes cells to stimuli leading to oxidative stress such as TNF, hypoxia or amyloid β-peptide, thereby contributing to disease pathogenesis. GENERAL SIGNIFICANCE Understanding the regulation of mGSH may provide novel insights to disease pathogenesis and toxicity and the opportunity to design therapeutic targets of intervention in cell death susceptibility and disease.

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Section: Introductionmentioning

confidence: 75%

Mitochondrial glutathione: Features, regulation and role in disease

Marı́

Morales

Colell

et al. 2013

Biochimica et Biophysica Acta (BBA) - General Subjects

173

117

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“…Tu and BFA have been previously used to induce ER stress . BFA, a macrocyclic lactone antibiotic synthesized from palmitate by a variety of fungi, induces endoplasmic reticulum (ER) and Golgi stress via the inhibition of ADP ribosylation factor (ARF), resulting in the reduction in coatomer protein assembly and the disruption of ER‐Golgi vesicular transport . Pretreatment of cells with ER stress inducers attenuated TRPC1‐mediated Ca 2+ entry in salivary gland cells.…”

Section: Discussionmentioning

confidence: 99%

TRPC1 expression and function inhibit ER stress and cell death in salivary gland cells

et al. 2018

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Disturbances in endoplasmic reticulum (ER) Ca2+ homeostasis have been associated with many diseases including loss of salivary glands. Although significant progress has been accomplished which led to the increase in our understanding of the cellular responses to ER stress, the factors/ion channels that could inhibit ER stress are not yet identified. Here we show that TRPC1 (transient receptor potential canonical 1) is involved in regulating Ca2+ homeostasis and loss of TRPC1 decreased ER Ca2+ levels, inhibited the unfolded protein response (UPR), that induced loss of salivary gland cells. We provide further evidence that ER stress inducing agents (Tunicamycin and Brefeldin A) disrupts Ca2+ homeostasis by directly inhibiting TRPC1-mediated Ca2+ entry, which led to ER stress in salivary gland cells. Moreover, induction of ER stress lead to an increase in CHOP expression, which decreased TRPC1 expression and subsequently attenuated autophagy along with increased apoptosis. Importantly, TRPC1−/− mice showed increased ER stress, increased immune cell infiltration, loss of Ca2+ homeostasis, decreased saliva secretion, and decreased salivary gland survival. Finally, restoration of TRPC1 not only maintained Ca2+ homeostasis, but inhibited ER stress that induced cell survival. Overall these results suggest a significant role of TRPC1 Ca2+ channels in ER stress and homeostatic function/survival of salivary gland cells.

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“…The ultimate outcome is an imbalance of the Bcl 2 family leading to permeabilization and release of cytochrome c and other intermembrane proteins. 35, 36, 37, 38, 39, 40, 41 …”

Section: Discussionmentioning

confidence: 99%

JNK interaction with Sab mediates ER stress induced inhibition of mitochondrial respiration and cell death

et al. 2014

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Our aim was to better understand the mechanism and importance of sustained c-Jun N-terminal kinase (JNK) activation in endoplasmic reticulum (ER) stress and effects of ER stress on mitochondria by determining the role of mitochondrial JNK binding protein, Sab. Tunicamycin or brefeldin A induced a rapid and marked decline in basal mitochondrial respiration and reserve-capacity followed by delayed mitochondrial-mediated apoptosis. Knockdown of mitochondrial Sab prevented ER stress-induced sustained JNK activation, impaired respiration, and apoptosis, but did not alter the magnitude or time course of activation of ER stress pathways. P-JNK plus adenosine 5′-triphosphate (ATP) added to isolated liver mitochondria promoted superoxide production, which was amplified by addition of calcium and inhibited by a blocking peptide corresponding to the JNK binding site on Sab (KIM1). This peptide also blocked tunicamycin-induced inhibition of cellular respiration. In conclusion, ER stress triggers an interaction of JNK with mitochondrial Sab, which leads to impaired respiration and increased mitochondrial reactive oxygen species, sustaining JNK activation culminating in apoptosis.

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Regulation of brefeldin A-induced ER stress and apoptosis by mitochondrial NADP+-dependent isocitrate dehydrogenase

Cited by 54 publications

References 24 publications

Mitochondrial glutathione: Features, regulation and role in disease

Mitochondrial glutathione: Features, regulation and role in disease

TRPC1 expression and function inhibit ER stress and cell death in salivary gland cells

JNK interaction with Sab mediates ER stress induced inhibition of mitochondrial respiration and cell death

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