Lactylation: a Passing Fad or the Future of Posttranslational Modification

Inflammation, Journal Year: 2022, Volume and Issue: 45(4), P. 1419 - 1429

Published: Feb. 27, 2022

Lactate is a glycolytic product and significant energy source. Moreover, it regulates gene transcription via lactylation of histones non-histone proteins, i.e., novel posttranslational modification. This review summarizes recent advances related to in lactate metabolism diseases. Notably, plays vital role cancer, inflammation, regeneration; however, the specific mechanism remains unclear. Histone oncogenic processes by targeting inflammation macrophage activation. Eventually, we identified research gaps recommended several primary directions for further studies.

Language: Английский

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Lactate as a myokine and exerkine: drivers and signals of physiology and metabolism

Journal of Applied Physiology, Journal Year: 2023, Volume and Issue: 134(3), P. 529 - 548

Published: Jan. 12, 2023

No longer viewed as a metabolic waste product and cause of muscle fatigue, contemporary view incorporates the roles lactate in metabolism, sensing signaling normal well pathophysiological conditions. Lactate exists millimolar concentrations muscle, blood, other tissues can rise more than an order magnitude result increased production clearance limitations. exerts its powerful driver-like influence by mass action, redox change, allosteric binding, mechanisms described this article. Depending on condition, such during rest exercise, following carbohydrate nutrition, injury, or pathology, serve myokine exerkine with autocrine-, paracrine-, endocrine-like functions that have important basic translational implications. For instance, is: involved reproductive biology, fueling heart, adaptation, brain executive function, growth development, treatment for inflammatory also works many factors controlling cardiac output pulmonary ventilation exercise. Ironically, be disruptive processes insulin secretion when insertion transporters into pancreatic β-cell membranes is not suppressed, carcinogenesis suppress are inhibited, whereas promote upregulated. areas intermediary mitochondrial biogenesis, neurobiology, gut physiology, appetite regulation, overall health vigor. The various reviewed.NEW & NOTEWORTHY relatively new rapidly changing field. As physiological signal both independently concert signals. operates via covalent binding canonical signaling, lactylation DNA. element feedback loops cardiopulmonary regulation. From conception through aging only exerkine, but it certainly deserves consideration signal.

Language: Английский

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Ubiquitous protein lactylation in health and diseases

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: Feb. 5, 2024

Abstract For decades, lactate has been considered a byproduct of glycolysis. The shuttle hypothesis shifted the paradigm, demonstrating that not only plays important roles in cellular metabolism but also communications, which can transcend compartment barriers and occur within among different cells, tissues organs. Recently, discovery induce novel post-translational modification, named lysine lactylation (Kla), brings forth new avenue to study nonmetabolic functions for lactate, inspired ‘gold rush’ academic commercial interest. Zhang et al. first showed Kla is manifested histones as epigenetic marks, then mounting evidences demonstrated occurs diverse non-histone proteins. widespread faithfully orchestrates numerous biological processes, such transcription, inflammatory responses. Notably, dysregulation touches myriad pathological processes. In this review, we comprehensively reviewed curated existing literature retrieve identified sites on both proteins summarized recent major advances toward its regulatory mechanism. We thoroughly investigated function underlying signaling pathway summarize how regulates various processes normal physiological states. addition, further highlight effects development human diseases including inflammation response, tumorigenesis, cardiovascular nervous system other complex diseases, might potentially contribute deeply understanding interpreting mechanism pathogenicity. Graphical

Language: Английский

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Histone lactylation: from tumor lactate metabolism to epigenetic regulation

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(5), P. 1833 - 1854

Published: Jan. 1, 2024

The Warburg Effect is one of the most well-known cancer hallmarks.This metabolic pattern centered on lactate has extremely complex effects various aspects tumor microenvironment, including remodeling, immune suppression, cell migration, and drug resistance development.Based accumulating evidence, metabolites are likely to participate in regulation biological processes microenvironment form a feedback loop.Therefore, further revealing key mechanism lactate-mediated oncological reasonable scientific idea.The discovery refinement histone lactylation recent years laid firm foundation for above idea.Histone post-translational modification that occurs at lysine sites histones.Specific enzymes, known as "writers" "erasers", catalyze addition or removal, respectively, lactacyl group target sites.An increasing number investigations have reported this multiple cellular procedures.In review, we discuss close connection between series tumorigenesis, infiltration, energy metabolism.Finally, review provides insightful perspectives, identifying promising avenues exploration potential clinical application field research.

Language: Английский

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Histone lactylation promotes malignant progression by facilitating USP39 expression to target PI3K/AKT/HIF-1α signal pathway in endometrial carcinoma

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: March 8, 2024

Abstract Histone lactylation has been reported to involve in tumorigenesis and development. However, its biological regulatory mechanism endometrial carcinoma (EC) is yet be detail. In the present study, we evaluated modification levels of global EC tissues by immunohistochemistry western blot, it was elevated. The non-metabolizable glucose analog 2-deoxy-d-glucose (2-DG) oxamate treatment could decrease level so as inhibit proliferation migration ability, induce apoptosis significantly, arrest cell cycle cells. Mechanically, histone stimulated USP39 expression promote tumor progression. Moreover, activated PI3K/AKT/HIF-1α signaling pathway via interacting with stabilizing PGK1 stimulate glycolysis. results study suggest that plays an important role progression promoting malignant behavior cells, thus providing insights into potential therapeutic strategies for cancer.

Language: Английский

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