Protein Lactylation Induced by Neural Excitation

Hagihara, Hideo; Shoji, Hirotaka; Otabi, Hikari; Toyoda, Atsushi; Katoh, K.; Namihira, Masakazu; Miyakawa, Tsuyoshi

doi:10.2139/ssrn.3831463

Cited by 10 publications

(15 citation statements)

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“…Lactoylglytathione is generated through the glyoxalase pathway and can be further hydrolyzed by glyoxalase 2 (GLO2), cycling glutathione (GSH), and generating d -lactate (Figure A). Increased l -lactate is suggested to repress the activity of GLO2 and thus lead to the elevation of lactoylglutathione levels and a marked increase in lysine lactylation. , GLO2-/- cells displayed a relative decrease in glycolytic metabolites downstream of glyceraldehyde-3P, the starting point for the glyoxalase pathway, suggesting a possible regulatory feedback for glycolysis . We focused on l -lactate-induced lysine lactylation in the current study; however, rather than being exclusive, it has been suggested that lactylation derived from l -lactate and lactoylglutathione may coexist .…”

Section: Discussionmentioning

confidence: 95%

“…Lysine lactylation has been identified as a novel PTM on human and mouse histone proteins recently . It can be stimulated by exogenous or glucose-derived endogenous lactate and has been associated with the modulation of gene transcription and the glycolysis pathway. , Although promoting gene transcription is similar to histone acetylation, histone lactylation has distinct temporal dynamics from acetylation as revealed by bacterially exposed M1 macrophages and quantitative proteomics analyses . Proteome-wide studies demonstrated the presence and prevalence of lysine lactylation in human, mouse, and plant-fungal pathogen B.…”

Section: Discussionmentioning

confidence: 99%

“…Proteome-wide studies demonstrated the presence and prevalence of lysine lactylation in human, mouse, and plant-fungal pathogen B. cinerea on both histone and nonhistone proteins. ,,, Unfortunately, no study focusing on protein lactylation in plants, especially in cereal crops, has been reported until now. Rice (O.…”

Section: Discussionmentioning

confidence: 99%

“…The level of Kla is dependent on the intracellular concentrations of lactate in a dose-dependent fashion associated with the glycolysis pathway . Inhibition of glycolysis has been demonstrated to reduce the Kla level; however, exogenous sources, such as the level of glucose, could also affect the degree of the cellular lactylation level. , …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Comprehensive Analysis of Lysine Lactylation in Rice (Oryza sativa) Grains

Meng

Baine

Yan

et al. 2021

J. Agric. Food Chem.

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Protein lysine lactylation is a new post-translational modification (PTM) prevalently found in fungi and mammalian cells that directly stimulates gene transcription and regulates the glycolytic flux. However, lysine lactylation sites and regulations remain largely unexplored, especially in cereal crops. Herein, we report the first global lactylome profile in rice, which effectively identified 638 lysine lactylation sites across 342 proteins in rice grains. Functional annotations demonstrated that lysine lactylation was enriched in proteins associated with central carbon metabolism and protein biosynthesis. We also observed that proteins serving as nutrition reservoirs in rice grains were frequently targeted by lactylation. Homology analyses indicated that lactylation was conserved on both histone and nonhistone proteins across plants, human cells, and fungi. In addition to lactylation, additional types of acylations could co-occur in many proteins at identical lysine residues, indicating potential cross-talks between these modifications. Our study provided a comprehensive profile of protein lysine lactylation in cereal crop grains.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comprehensive Analysis of Lysine Lactylation in Rice (Oryza sativa) Grains

Meng

Baine

Yan

et al. 2021

J. Agric. Food Chem.

View full text Add to dashboard Cite

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“…Notably, lactate can fulfill diverse roles in the target cells, including as an energy substrate or modulating cellular redox state, by directly activating (e.g., GPR81/HCAR1) or modulating receptors (e.g., NMDARs) and affecting various signaling (e.g., calcium) (Barros, 2013). Neuronal activity‐related and animal stress‐induced protein lactylation were also recently shown to depend on lactate availability (Hagihara et al, 2021), extending the range of lactate's functions to epigenetic regulation. Additional roles for lactate (and other metabolites) are likely.…”

Section: Challenges In Interpreting Astrocyte Functionmentioning

confidence: 99%

A perspective on astrocyte regulation of neural circuit function and animal behavior

Hirrlinger

Nimmerjahn

2022

Glia

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Studies over the past two decades have demonstrated that astrocytes are tightly associated with neurons and play pivotal roles in neural circuit development, operation, and adaptation in health and disease. Nevertheless, precisely how astrocytes integrate diverse neuronal signals, modulate neural circuit structure and function at multiple temporal and spatial scales, and influence animal behavior or disease through aberrant excitation and molecular output remains unclear. This Perspective discusses how new and state‐of‐the‐art approaches, including fluorescence indicators, opto‐ and chemogenetic actuators, genetic targeting tools, quantitative behavioral assays, and computational methods, might help resolve these longstanding questions. It also addresses complicating factors in interpreting astrocytes' role in neural circuit regulation and animal behavior, such as their heterogeneity, metabolism, and inter‐glial communication. Research on these questions should provide a deeper mechanistic understanding of astrocyte‐neuron assemblies' role in neural circuit function, complex behaviors, and disease.

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Lactate: a pearl dropped in the ocean—an overlooked signal molecule in physiology and pathology

Liu

et al. 2022

Cell Biology International

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Lactate, once recognized as a wasty product from anaerobic glycolysis, is proved to be a pivotal signal molecule. Lactate accumulation occurs in diverse physiological and pathological settings due to the imbalance between lactate production and clearance. Under the condition with drastic changes in local microenvironment, such as tumorigenesis, inflammation, and microbial infection, the glycolysis turns to be active in surrounding cells leading to increased lactate release. Meanwhile, lactate can be utilized by these cells as an energy substrate and acts as a signal molecule to regulate cell functions through receptor‐dependent or independent pathways. In this review, we tended to tease out the contribution of lactate in tumor progression and immunomodulation. And we also discussed the accessory role of lactate, beyond as the energy source only, in the growth of invading pathogens.

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Protein Lactylation Induced by Neural Excitation

Cited by 10 publications

References 0 publications

Comprehensive Analysis of Lysine Lactylation in Rice (Oryza sativa) Grains

Comprehensive Analysis of Lysine Lactylation in Rice (Oryza sativa) Grains

A perspective on astrocyte regulation of neural circuit function and animal behavior

Lactate: a pearl dropped in the ocean—an overlooked signal molecule in physiology and pathology

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