Functions and Mechanisms of Lysine Glutarylation in Eukaryotes

Xie, Longxiang; Xiao, Yafei; Meng, Fucheng; Li, Yongqiang; Shi, Zhenyu; Qian, Keli

doi:10.3389/fcell.2021.667684

Cited by 15 publications

(13 citation statements)

References 92 publications

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“…We first performed whole protein lysate western blot analysis with a pan-lysine-glutarylation (K-glu) antibody (Tan et al ., 2014; Xie et al ., 2021) and found that glutarylation is clearly detectable in CD8 + T cells (Figure 4B). We also found that glutarylation patterns change strikingly upon CD8 + T cell activation (Figure 4B).…”

Section: Resultsmentioning

confidence: 99%

Glutarate regulates T cell function and metabolism

Minogue

Cunha

Quaranta

et al. 2022

Preprint

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T cell function is influenced by several metabolites; some acting through enzymatic inhibition of α-KG-dependent dioxygenases (αKGDDs), others, through post-translational modification of lysines in important targets. We show here that glutarate, a product of amino acid catabolism, has the capacity to do both, with effects on T cell function and differentiation. Glutarate exerts those effects through αKGDD inhibition and through direct regulation of T cell metabolism via post-translational modification of the pyruvate dehydrogenase E2 subunit. Diethyl-glutarate, a cell-permeable form of glutarate, alters CD8+T cell differentiation and increases cytotoxicity against target cells.In vivoadministration of the compound reduces tumor growth and is correlated with increased levels of both peripheral and intratumoral cytotoxic CD8+T cells. These results demonstrate that glutarate regulates both T cell metabolism and differentiation, with a potential role in the improvement of T cell immunotherapy.

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Section: Resultsmentioning

confidence: 99%

Glutarate regulates T cell function and metabolism

Minogue

Cunha

Quaranta

et al. 2022

Preprint

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“…34,35 Lysine (K) glutarylation is known to be associated with cellular functions such as metabolic processes, oxidative damage, and other mitochondrial functions. 36,37 We identified 1058 unique glutarylation sites mapping to 836 proteins in this study. The examples include several proteins of the early transcribed membrane protein (ETRAMP) family, including erythrocyte membrane protein 3 (PY05500 at K15, PY04042 at K863, PY06125 at K770), erythrocyte membrane-associated antigen (PY06959 at K460), erythrocyte membrane-associated antigen, putative (PY06110 at K125), and ETRAMP (PY00205 at K17).…”

Section: ■ Resultsmentioning

confidence: 99%

Dissecting Plasmodium yoelii Pathobiology: Proteomic Approaches for Decoding Novel Translational and Post-Translational Modifications

et al. 2022

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Malaria is a vector-borne disease. It is caused by Plasmodium parasites. Plasmodium yoelii is a rodent model parasite, primarily used for studying parasite development in liver cells and vectors. To better understand parasite biology, we carried out a high-throughput-based proteomic analysis of P. yoelii. From the same mass spectrometry (MS)/MS data set, we also captured several post-translational modified peptides by following a bioinformatics analysis without any prior enrichment. Further, we carried out a proteogenomic analysis, which resulted in improvements to some of the existing gene models along with the identification of several novel genes. Analysis of proteome and post-translational modifications (PTMs) together resulted in the identification of 3124 proteins. The identified PTMs were found to be enriched in mitochondrial metabolic pathways. Subsequent bioinformatics analysis provided an insight into proteins associated with metabolic regulatory mechanisms. Among these, the tricarboxylic acid (TCA) cycle and the isoprenoid synthesis pathway are found to be essential for parasite survival and drug resistance. The proteogenomic analysis discovered 43 novel protein-coding genes. The availability of an in-depth proteomic landscape of a malaria pathogen model will likely facilitate further molecular-level investigations on pre-erythrocytic stages of malaria.

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“… 491 SIRT5 defects lead to an increase in succinyl‐coA in the heart. 504 Elevated levels of Ksucc can lead to hypertrophic obstructive cardiomyopathy, 528 while oxidative stress caused by Kglu may be an important mechanism for inducing CVDs. 546 A high‐fat diet causes adverse effects on cardiovascular health, especially under stressful conditions.…”

Section: Other Scfa Modificationsmentioning

confidence: 99%

“…Kglu, a reversible, dynamic and conserved modification, is produced by covalently binding glutaryl groups to lysine residues 504 and occurs mainly in mitochondria 532 . Kglu plays an important role in regulating protein structural changes, 532 oxidative damage, 533 mitochondrial functions, 534 and sperm motility 535 …”

Section: Other Scfa Modificationsmentioning

confidence: 99%

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

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Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

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Functions and Mechanisms of Lysine Glutarylation in Eukaryotes

Cited by 15 publications

References 92 publications

Glutarate regulates T cell function and metabolism

Glutarate regulates T cell function and metabolism

Dissecting Plasmodium yoelii Pathobiology: Proteomic Approaches for Decoding Novel Translational and Post-Translational Modifications

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

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