Stressed to death: Mitochondrial stress responses connect respiration and apoptosis in cancer

Winter, Jacob M.; Yadav, Tarun; Rutter, Jared

doi:10.1016/j.molcel.2022.07.012

Cited by 39 publications

(19 citation statements)

References 93 publications

(119 reference statements)

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“…Meanwhile, we cannot rule out the possibility that other sirtuins function in oxidative stress and contribute to the effect of mitochondria function. Mitochondria play a curial role in apoptosis by activating mitochondrial outer membrane permeabilization, which leads to the release of caspase-activating molecules, caspase-independent death effectors, and disruption of ATP production . Despite the central role for mitochondria in the control of apoptosis, surprisingly little is known about how nuclear SIRT1 participates in apoptotic programs.…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondria play a curial role in apoptosis by activating mitochondrial outer membrane permeabilization, which leads to the release of caspaseactivating molecules, caspase-independent death effectors, and disruption of ATP production. 49 Despite the central role for mitochondria in the control of apoptosis, surprisingly little is known about how nuclear SIRT1 participates in apoptotic programs. It was observed that the SIRT1/PGC-1α/P53 Lys382 signaling pathway was involved in the activation of oxidative mitochondrial apoptosis signaling.…”

Section: ■ Discussionmentioning

confidence: 99%

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Reactive Oxygen Species Control Osteoblast Apoptosis through SIRT1/PGC-1α/P53^Lys382 Signaling, Mediating the Onset of Cd-Induced Osteoporosis

Zhou

Liu

et al. 2023

J. Agric. Food Chem.

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The imbalance between osteogenesis and osteoclastogenesis is a feature of bone metabolic disease. Cadmium (Cd) exposure causes human bone loss and osteoporosis (OP) through bioaccumulation of the food chain. However, the impact of Cd on bone tissues and the underlying molecular mechanisms are not well-characterized. In the current study, we found that the Cd concentration in bone tissues of OP patients was higher than normal subjects; meanwhile, the nuclear silent information regulator of transcription 1 (SIRT1) protein expression level was significantly decreased, which is a new star molecule to treat OP. It is further revealed that SIRT1 activation markedly reprograms bone metabolic and stress-response pathways that incline with osteoblast (OB) apoptosis. Suppressing reactive oxygen species (ROS) release with N-acetyl-l-cysteine (NAC) abolished Cd-induced reduction of SIRT1 protein, deacetylation of P53, OB apoptosis, and attenuated OP. Conversely, overexpression of SIRT1 suppressed Cd-induced ROS release. SIRT1 overexpression in vivo and in vitro dampened PGC-1α protein, acetylation of P53 at lysine 382, and caspase-dependent apoptosis. These results reveal that ROS/SIRT1 controls P53 acetylation and coordinates OB apoptosis involved in the onset of OP.

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Section: Discussionmentioning

confidence: 99%

Section: ■ Discussionmentioning

confidence: 99%

Reactive Oxygen Species Control Osteoblast Apoptosis through SIRT1/PGC-1α/P53^Lys382 Signaling, Mediating the Onset of Cd-Induced Osteoporosis

Zhou

Liu

et al. 2023

J. Agric. Food Chem.

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“…Afterwards, the released Cytc interacted with Apaf-1 and formed an apoptotic complex with the assistance of ATP and dATP. Then the apoptotic complex recruited and activated pro-caspase9 to assemble the Caspase9 holoenzyme, which started effector Caspase3 and caspase7, initiated caspase cascade reaction, and finally led to cell apoptosis [ 55 – 57 ]. We found that after MR infusion, the expression of Pro-apoptotic proteins Cytc, Caspase-3, and Bax decreased significantly.…”

Section: Discussionmentioning

confidence: 99%

Effects of Malate Ringer's solution on myocardial injury in sepsis and enforcement effects of TPP@PAMAM-MR

et al. 2022

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Background Myocardial dysfunction played a vital role in organ damage after sepsis. Fluid resuscitation was the essential treatment in which Lactate Ringer's solution (LR) was commonly used. Since LR easily led to hyperlactatemia, its resuscitation effect was limited. Malate Ringer's solution (MR) was a new resuscitation crystal liquid. Whether MR had a protective effect on myocardial injury in sepsis and the relevant mechanism need to be studied. Methods The cecal ligation and puncture (CLP) inducing septic model and lipopolysaccharide (LPS) stimulating cardiomyocytes were used, and the cardiac function, the morphology and function of mitochondria were observed. The protective mechanism of MR on myocardial injury was explored by proteomics. Then the effects of TPP@PAMAM-MR, which consisted of the mitochondria- targeting polymer embodied malic acid, was further observed. Results Compared with LR, MR resuscitation significantly prolonged survival time, improved the cardiac function, alleviated the damages of liver, kidney and lung following sepsis in rats. The proteomics of myocardial tissue showed that differently expressed proteins between MR and LR infusion involved oxidative phosphorylation, apoptosis. Further study found that MR decreased ROS, improved the mitochondrial morphology and function, and ultimately enhanced mitochondrial respiration and promoted ATP production. Moreover, MR infusion decreased the expression of apoptosis-related proteins and increased the expression of anti-apoptotic proteins. TPP@PAMAM@MA was a polymer formed by wrapping l-malic acid with poly amido amine (PAMAM) modified triphenylphosphine material. TPP@PAMAM-MR (TPP-MR), which was synthesized by replacing the l-malic acid of MR with TPP@PAMAM@MA, was more efficient in targeting myocardial mitochondria and was superior to MR in protecting the sepsis-inducing myocardial injury. Conclusion MR was suitable for protecting myocardial injury after sepsis. The mechanism was related to MR improving the function and morphology of cardiomyocyte mitochondria and inhibiting cardiomyocyte apoptosis. The protective effect of TPP-MR was superior to MR.

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“…Under chronic stress, ISR leads to apoptosis. This pathway intersects at the eukaryotic initiation factor subunit eIF2α to slow translation and protein synthesis while allowing adaptive mechanisms to continue [ 18 , 19 ]. Various physiological and pathological changes, including endoplasmic reticulum stress, amino acid deficiency, viral infection, oxidative stress, etc., can activate ISR.…”

Section: Mechanism Of Copper Compound-induced Cell Deathmentioning

confidence: 99%

Potential of Copper and Copper Compounds for Anticancer Applications

Wang

Chen

et al. 2023

Pharmaceuticals

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Inducing cancer cell death has always been a research hotspot in life sciences. With the continuous deepening and diversification of related research, the potential value of metal elements in inducing cell death has been explored. Taking iron as an example, ferroptosis, mainly characterized by increasing iron load and driving the production of large amounts of lipid peroxides and eventually leading to cell death, has recently attracted great interest in the cancer research community. After iron, copper, a trace element, has received extensive attention in cell death, especially in inducing tumor cell death. Copper and its complexes can induce autophagy or apoptosis in tumor cells through a variety of different mechanisms of action (activation of stress pathways, arrest of cell cycle, inhibition of angiogenesis, cuproptosis, and paraptosis), which are promising in cancer therapy and have become new hotspots in cancer treatment research. This article reviews the main mechanisms and potential applications of novel copper and copper compound-induced cell death, focusing on copper compounds and their anticancer applications.

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Stressed to death: Mitochondrial stress responses connect respiration and apoptosis in cancer

Cited by 39 publications

References 93 publications

Reactive Oxygen Species Control Osteoblast Apoptosis through SIRT1/PGC-1α/P53^Lys382 Signaling, Mediating the Onset of Cd-Induced Osteoporosis

Reactive Oxygen Species Control Osteoblast Apoptosis through SIRT1/PGC-1α/P53^Lys382 Signaling, Mediating the Onset of Cd-Induced Osteoporosis

Effects of Malate Ringer's solution on myocardial injury in sepsis and enforcement effects of TPP@PAMAM-MR

Potential of Copper and Copper Compounds for Anticancer Applications

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Stressed to death: Mitochondrial stress responses connect respiration and apoptosis in cancer

Cited by 39 publications

References 93 publications

Reactive Oxygen Species Control Osteoblast Apoptosis through SIRT1/PGC-1α/P53Lys382 Signaling, Mediating the Onset of Cd-Induced Osteoporosis

Reactive Oxygen Species Control Osteoblast Apoptosis through SIRT1/PGC-1α/P53Lys382 Signaling, Mediating the Onset of Cd-Induced Osteoporosis

Effects of Malate Ringer's solution on myocardial injury in sepsis and enforcement effects of TPP@PAMAM-MR

Potential of Copper and Copper Compounds for Anticancer Applications

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Product

Resources

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Reactive Oxygen Species Control Osteoblast Apoptosis through SIRT1/PGC-1α/P53^Lys382 Signaling, Mediating the Onset of Cd-Induced Osteoporosis

Reactive Oxygen Species Control Osteoblast Apoptosis through SIRT1/PGC-1α/P53^Lys382 Signaling, Mediating the Onset of Cd-Induced Osteoporosis