Malonate induces the assembly of cytoplasmic stress granules

Xue, Fu Shan; Gao, Xingjie; Ge, Lin; Cui, Xiaoteng; Su, Chao; Yang, Wendong; Sun, Xiaoming; Zhang, Wei; Yao, Zhi; Yang, Xi; Yang, Jie

doi:10.1002/1873-3468.12049

Cited by 14 publications

(5 citation statements)

References 41 publications

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“…Hypotaurine is an intermediate in the normal synthesis of taurine [20] and can act as an antioxidant involved in cellular defense against oxidative stress [20–22]. Histamine is reportedly associated with allergies and inflammation [23], propionate is a major microbial fermentation metabolite present in the human gut and that provides putative health effects [24], and malonate induces mitochondrial stress [25]. Additionally, the therapeutic potential of carnosine supplementation is reportedly associated with clinical consequences in a number of diseases [26].…”

Section: Discussionmentioning

confidence: 99%

Metabolomic profiling reveals salivary hypotaurine as a potential early detection marker for medication-related osteonecrosis of the jaw

Yatsuoka

Ueno

Miyano³

et al. 2019

PLoS ONE

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Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse event of bone-modifying agents used to prevent bone complications in cancer patients with bone metastasis. Currently, early treatment is the only way to prevent further progression, as the pathogenesis of MRONJ has not yet been elucidated, and a standard treatment has not been established. The aim of this study was to identify a marker for early detection marker of MRONJ by exploring substances in saliva specific to MRONJ at an early stage. We collected salivary samples from 17 patients with MRONJ and conducted metabolomic analyses using capillary electrophoresis mass spectrometry for non-targeted analysis of hydrophilic metabolites. In the screening cohort, we compared the saliva of patients with stage ≥1 advanced MRONJ ( n = 9) with that of controls without MRONJ before chemotherapy ( n = 9). The top 5 most elevated salivary metabolites were histamine, 3-(4-hydroxyphenyl)propionate, malonate, carnosine, and hypotaurine. In the validation cohort, we analyzed additional patients with stage ≥1 advanced MRONJ ( n = 8) and controls without MRONJ after chemotherapy ( n = 9), confirming a significant 2.28-fold elevation in the salivary concentration of hypotaurine. These results revealed elevated salivary hypotaurine concentration as a potential marker for the early detection of MRONJ.

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Section: Discussionmentioning

confidence: 99%

Metabolomic profiling reveals salivary hypotaurine as a potential early detection marker for medication-related osteonecrosis of the jaw

Yatsuoka

Ueno

Miyano³

et al. 2019

PLoS ONE

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“…Stress granules are an important part of RNA metabolism during cellular stress and are composed primarily of RNAs and RBPs. Stress granules can be induced by various cellular stressors, including glucose starvation, oxidative stress, viral infection, and mitochondrial dysfunction (Piotrowska et al, 2010 ; Fu et al, 2016 ; Palangi et al, 2017 ; Moon and Parker, 2018 ). Once stress is relieved, the stress granule can be either disassembled or degraded by autophagy.…”

Section: Common Mechanisms Of Neurodegeneration In Als and Ftdmentioning

confidence: 99%

DNA Damage and Repair Deficiency in ALS/FTD-Associated Neurodegeneration: From Molecular Mechanisms to Therapeutic Implication

Wang

Manohar

Britz

et al. 2021

Front. Mol. Neurosci.

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Emerging studies reveal that neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), are commonly linked to DNA damage accumulation and repair deficiency. Neurons are particularly vulnerable to DNA damage due to their high metabolic activity, relying primarily on oxidative phosphorylation, which leads to increased reactive oxygen species (ROS) generation and subsequent DNA damage. Efficient and timely repair of such damage is critical for guarding the integrity of genomic DNA and for cell survival. Several genes predominantly associated with RNA/DNA metabolism have been implicated in both ALS and FTD, suggesting that the two diseases share a common underlying pathology with varied clinical manifestations. Recent studies reveal that many of the gene products, including RNA/DNA binding proteins (RBPs) TDP-43 and FUS are involved in diverse DNA repair pathways. A key question in the etiology of the ALS/FTD spectrum of neurodegeneration is the mechanisms and pathways involved in genome instability caused by dysfunctions/mutations of those RBP genes and their consequences in the central nervous system. The understanding of such converging molecular mechanisms provides insights into the underlying etiology of the rapidly progressing neurodegeneration in ALS/FTD, while also revealing novel DNA repair target avenues for therapeutic development. In this review, we summarize the common mechanisms of neurodegeneration in ALS and FTD, with a particular emphasis on the DNA repair defects induced by ALS/FTD causative genes. We also highlight the consequences of DNA repair defects in ALS/FTD and the therapeutic potential of DNA damage repair-targeted amelioration of neurodegeneration.

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“…Malonate, a classic competitive inhibitor of the respiratory electron transport chain, induces mitochondrial stress and inhibits mitochondrial respiration [ 92 , 93 ]. It has been reported that malonate induces SG aggregation through 4E-BP1-mediated inactivation of the eIF4E pathway, which may inhibit apoptosis in HeLa cells [ 94 ]. Like malonate, selenium, an essential micronutrient that promotes the production of reactive oxygen species (ROS) for targeting tumour cells [ 31 ], induces SG assembly by destroying the eIF4F complex via the dephosphorylation of 4E-BP1 [ 39 ].…”

Section: Small Molecules Targeting Sgsmentioning

confidence: 99%