Lactate is a bridge linking glycolysis and autophagy through lactylation

Sun, Weixia; Jia, Mengshu; Feng, Yaoyu; Cheng, Xiawei

doi:10.1080/15548627.2023.2246356

Cited by 13 publications

(7 citation statements)

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“…Many studies had confirmed that cells utilize glucose mainly through glycolysis, aerobic oxidation and glycogen synthesis, and lactate was one of the metabolic products of glycolysis ( Sun et al, 2023 ). In our lactate content determination experiments, the cells were cultured under anaerobic conditions.…”

Section: Resultsmentioning

confidence: 99%

Investigation of anti-diabetic effect of a novel coenzyme Q10 derivative

Tan,

Yang,

et al. 2023

Front. Chem.

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Introduction: The rising incidence of type 2 diabetes has seriously affected international public health. The search for more drugs that can effectively treat diabetes has become a cutting-edge trend in research. Coenzyme Q10 (CoQ10) has attracted much attention in the last decade due to its wide range of biological activities. Many researchers have explored the clinical effects of CoQ10 in patients with type 2 diabetes. However, CoQ10 has low bio-availability due to its high lipophilicity. Therefore, we have structurally optimized CoQ10 in an attempt to exploit the potential of its pharmacological activity.Methods: A novel coenzyme Q10 derivative (L-50) was designed and synthesized by introducing a group containing bromine atom and hydroxyl at the terminal of coenzyme Q10 (CoQ10), and the antidiabetic effect of L-50 was investigated by cellular assays and animal experiments.Results: Cytotoxicity results showed that L-50 was comparatively low toxicity to HepG2 cells. Hypoglycemic assays indicated that L-50 could increase glucose uptake in IR-HepG2 cells, with significantly enhanced hypoglycemic capacity compared to the CoQ10. In addition, L-50 improved cellular utilization of glucose through reduction of reactive oxygen species (ROS) accumulated in insulin-resistant HepG2 cells (IR-HepG2) and regulation of JNK/AKT/GSK3β signaling pathway, resulting in hypoglycemic effects. Furthermore, the animal experiments demonstrated that L-50 could restore the body weight of HFD/STZ mice. Notably, the findings suggested that L-50 could improve glycemic and lipid metabolism in HFD/STZ mice. Moreover, L-50 could increase fasting insulin levels (FINS) in HFD/STZ mice, leading to a decrease in fasting blood glucose (FBG) and hepatic glycogen. Furthermore, L-50 could recover triglycerides (TG), total cholesterol (T-CHO), lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) levels in HFD/STZ mice.Discussion: The addition of a bromine atom and a hydroxyl group to CoQ10 could enhance its anti-diabetic activity. It is anticipated that L-50 could be a promising new agent for T2DM.

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Section: Resultsmentioning

confidence: 99%

Investigation of anti-diabetic effect of a novel coenzyme Q10 derivative

Tan,

Yang,

et al. 2023

Front. Chem.

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“…It has been reported that LDHA regulated lactate production to in uence histone lysine lactylation and acetylation [33][34][35] . Here, we observed that the levels of lactylated histone H3K18 (H3K18Lac) and acetylated H3K18 (H3K18Ac) were increased in Th1 cells differentiation with poly(I:C) stimulation compared with mock control (Fig.…”

Section: Rig-i De Ciency Relieved Eae Mice Model and Lupus-like Mice ...mentioning

confidence: 99%

Endogenous retrovirus promotes the aberrant T cell differentiation in systemic lupus erythematosus via RIG-I pathway

Zhao,

Min,

et al. 2024

Preprint

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The dysregulated differentiation of T lymphocyte play an important role in systemic lupus erythematosus (SLE). However, the underlying mechanism remains unclear. Here, we showed that many transcripts derived from human endogenous retroviruses (HERVs) were highly expressed in CD4+ T cells from SLE patients due to DNA hypomethylation, some of which were characterized by double strand RNAs (dsRNAs). Excessive dsRNAs promoted Th1/Th17 differentiation and inhibited Treg cell differentiation via the activation of dsRNA sensor retinoic acid-inducible gene I (RIG-I). And T cell-specific ablation of RIG-I alleviated disease progression in experimental autoimmune encephalomyelitis (EAE) mice model and lupus-like mice model. Importantly, we demonstrated that dsRNA-activated RIG-I protein bind lactate dehydrogenase A (LDHA) and regulate histone lysine 18 lactylation (H3K18Lac) and acetylation (H3K18Ac) modifications in T cell differentiation via changing lactate level. Collectively, our findings uncover a novel role and mechanism of HERVs and RIG-I in regulating the aberrant differentiation of T cells in SLE patients.

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“…It has also been suggested that high lactate mediates PIK3C3/VPS34 emulsification and induces autophagy, thereby promoting cancer progression. Lactate is a bridge linking glycolysis and autophagy [ 127 ]. Furthermore, canagliflozin (CAN) can inhibit glucose uptake and lactate release, and modulate autophagy at the same time, thus enhancing the radiosensitivity of HepG2 cells.…”

Section: Mechanisms Underlying Radioresistance Due To Hypoxia and Met...mentioning

confidence: 99%

Feedback loop between hypoxia and energy metabolic reprogramming aggravates the radioresistance of cancer cells

Shi,

Hu,

Zheng

et al. 2024

Exp Hematol Oncol

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Radiotherapy is one of the mainstream approaches for cancer treatment, although the clinical outcomes are limited due to the radioresistance of tumor cells. Hypoxia and metabolic reprogramming are the hallmarks of tumor initiation and progression and are closely linked to radioresistance. Inside a tumor, the rate of angiogenesis lags behind cell proliferation, and the underdevelopment and abnormal functions of blood vessels in some loci result in oxygen deficiency in cancer cells, i.e., hypoxia. This prevents radiation from effectively eliminating the hypoxic cancer cells. Cancer cells switch to glycolysis as the main source of energy, a phenomenon known as the Warburg effect, to sustain their rapid proliferation rates. Therefore, pathways involved in metabolic reprogramming and hypoxia-induced radioresistance are promising intervention targets for cancer treatment. In this review, we discussed the mechanisms and pathways underlying radioresistance due to hypoxia and metabolic reprogramming in detail, including DNA repair, role of cancer stem cells, oxidative stress relief, autophagy regulation, angiogenesis and immune escape. In addition, we proposed the existence of a feedback loop between energy metabolic reprogramming and hypoxia, which is associated with the development and exacerbation of radioresistance in tumors. Simultaneous blockade of this feedback loop and other tumor-specific targets can be an effective approach to overcome radioresistance of cancer cells. This comprehensive overview provides new insights into the mechanisms underlying tumor radiosensitivity and progression.

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Lactate is a bridge linking glycolysis and autophagy through lactylation

Cited by 13 publications

References 1 publication

Investigation of anti-diabetic effect of a novel coenzyme Q10 derivative

Investigation of anti-diabetic effect of a novel coenzyme Q10 derivative

Endogenous retrovirus promotes the aberrant T cell differentiation in systemic lupus erythematosus via RIG-I pathway

Feedback loop between hypoxia and energy metabolic reprogramming aggravates the radioresistance of cancer cells

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