adenosine triphosphate

Overview

Adenosine triphosphate (ATP) is a ubiquitous adenine nucleotide that serves as the principal immediate energy currency of living cells. It is central to cellular bioenergetics because hydrolysis of its terminal phosphate bond can be coupled to a wide range of endergonic processes, including biosynthesis, ion transport, mechanical work, and signal transduction. ATP is generated primarily through glycolysis and oxidative phosphorylation, and its intracellular abundance is tightly linked to mitochondrial function, oxygen consumption, and metabolic state.

Beyond its intracellular role, ATP also has important extracellular signaling functions. In the tumor and immune microenvironment, ATP can act as a danger-associated signal that influences dendritic cells, cytotoxic T cells, macrophages, and checkpoint inhibitor responses. In disease settings characterized by mitochondrial dysfunction, oxidative stress, cuproptosis, or altered autophagy and mitophagy, ATP levels are often used as a readout of cellular energetic integrity and treatment response.

Focus of Latest Publications

The recent studies provided here use ATP primarily as a biomarker and mechanistic endpoint for cellular energy metabolism, mitochondrial health, and immunogenic signaling.

Several papers focused on restoring ATP production in models of mitochondrial dysfunction and inflammatory injury. In acute lung injury, palladium-loaded siraitia grosvenorii carbon dots were reported to target mitochondria and increase ATP production and mitochondrial membrane potential, thereby repairing mitochondrial function in lipopolysaccharide-induced cells. In osteoarthritis, artificial mitochondria were described as ameliorating disease by restoring cellular energy metabolism homeostasis, with the authors emphasizing that pathological or aging-related mitochondrial dysfunction disrupts ATP synthesis and shifts metabolism toward catabolism. Similarly, in diabetic foot ulcer models, a metformin-containing adhesive polyethylene glycol hydrogel reduced glycolytic flux, lowered glucose uptake and consumption, increased ATP production, and restored oxygen consumption under lipopolysaccharide or Staphylococcal protein A stimulation, indicating a shift from glycolysis toward oxidative phosphorylation.

ATP was also used as a marker of tissue or organ energy status in metabolic disease. In recent-onset type 1 diabetes, hepatic adenosine triphosphate and inorganic phosphate concentrations were reported to be lower and to decline further early in disease. In post-myocardial infarction heart failure with reduced ejection fraction, Yangxinshi Tablet was reported to improve cardiac energy metabolism by inhibiting FOXO1/PDK4 signaling, enhancing TCA cycle activity, and elevating ATP production. In bed rest studies, reduced resting oxygen uptake and energy expenditure were interpreted as a recalibration of ATP supply to lower ATP demand. In placental trophoblast cells exposed to ox-LDL, mitochondrial fragmentation was associated with reduced ATP production and diminished mitochondrial membrane potential. In neurodegenerative and neuroprotective contexts, treatments such as β-asarone, Tenuifolin, YuanZhi Decoction, and C-phycocyanin were reported to restore ATP levels alongside improvements in cognitive function, oxidative stress, and cuproptosis-related markers.

A second group of studies used ATP depletion or ATP release as a mechanistic readout in cancer and immunology. In colorectal cancer, triterpenoids from quinoa bran induced immunogenic cell death, with enhanced calreticulin exposure and release of ATP and HMGB1, consistent with a vaccine-like effect. A ratio-tunable dual-peptide and ultrasound-assisted nanoplatform similarly promoted sonodynamic therapy-induced immunogenic cell death with ATP and HMGB1 release. In another colorectal cancer study, a Faecalibacterium prausnitzii enzyme depleted ATP levels in cancer cells and inhibited GTP-GDP exchange on Rab11a, reprogramming energy metabolism and PD-L1 trafficking to sensitize tumors to immunotherapy. In glioblastoma, nebivolol impaired Mitochondrial respiratory chain complex I activity, diminished ATP synthesis, and increased ROS, contributing to apoptosis. In prostate cancer, icariin was evaluated in relation to glycolysis using ATP among other metabolic readouts, and in a separate study a dual-function inhibitor reduced lactate and ATP levels while activating AMPK-linked apoptotic signaling. In melanoma and breast cancer membrane systems, inhibition of ectonucleotidase CD39 reduced ATP hydrolysis and partially reversed ATP-mediated effects on T cell activation and proliferation in an ATP-rich environment, underscoring the extracellular immunoregulatory role of ATP.

ATP also appeared in studies of metabolic reprogramming and microbial or biotechnological production systems. Aerobic cultivation of Lactococcus lactis increased intracellular ATP and the NAD+/NADH ratio, redirecting flux toward nisin production. In a study of creatine kinase monitoring, ATP served as an intermediate in a Fe3+-ATP-CK cascade-regulated fluorescent probe, illustrating its utility in enzymatic assays. A sweet-responsive magnetic metal-organic framework was developed for point-of-care ATP testing using a personal glucose meter, and another platform enabled simultaneous quantitative detection of ATP, uric acid, adenine, and creatinine in urine. In aqueous solution studies, ATP was included among biologically relevant phosphate salts used to examine diffusion and viscosity behavior.

Several studies linked ATP to mitochondrial rescue, autophagy, mitophagy, and bioenergetic crisis. RGFP966 in acute gouty arthritis increased ATP and mitochondrial membrane potential while promoting Pink1, Parkin, and LC3-II, consistent with enhanced mitophagy. In contrast, a calcium carbonate-based nanoreactor induced mitochondrial calcium overload, permeability transition pore opening, and precipitous ATP depletion, producing a “bioenergetic crisis” that reversed cisplatin resistance. BPM31510 increased the CoQ pool and raised ATP content in SH-SY5Y cells and in CoQ-deficient tissues, supporting improved mitochondrial electron transport. In cuproptosis-related neuroprotection, C-phycocyanin elevated ATP levels while restoring mitochondrial membrane potential and reducing oxidative stress. Intermittent fasting was also discussed as a regulator of autophagy through changes in ATP and ADP levels, acting through AMPK and sirtuin 1 and inhibiting mechanistic target of rapamycin kinase signaling.

Overall, these studies position ATP as both a functional metabolite and a sensitive indicator of mitochondrial performance, glycolytic versus oxidative metabolic balance, immunogenic cell death, and therapeutic response across inflammatory disease, neurodegeneration, metabolic disorders, and cancer.

Key Publications

• Jun Adhesive polyethylene glycol hydrogels with metformin enabling in-situ drug delivery reprogramming immuno-metabolism for tissue repair in diabetic foot ulcers. (Acta biomaterialia, 2026, PMID 42025984): "Under lipopolysaccharides (LPS) or Staphylococcal protein A (SpA) induced pro-inflammatory stimulation, the PEG/Met suppressed glycolytic flux, reduced glucose uptake and consumption, yet increased adenosine triphosphate (ATP) production and restored oxygen consumption, indicating a shift from glycolysis toward oxidative phosphorylation (OXPHOS)."
• Jun Systemic Inflammation and Peripheral T Cell Responses Associate With Hepatic Energy Metabolism in Recent-Onset Type 1 Diabetes. (Liver international : official journal of the International Association for the Study of the Liver, 2026, PMID 42130117): "People with type 1 diabetes feature lower concentrations of hepatic adenosine-triphosphate (ATP) and inorganic phosphate (Pi), which further decline during the early course of disease."
• May Triterpenoids from quinoa bran exert anti-colorectal cancer effects via oxidative stress-mediated apoptosis and immune reactivation. (Food & function, 2026, PMID 42093524): "as evidenced by enhanced calreticulin exposure and the release of ATP and high mobility group box 1 (HMGB1), eliciting a robust "vaccine-like effect"."
• May Icariin suppresses glycolysis in prostate cancer by upregulating ALKBH5 to mediate EARS2 m6A demethylation. (Journal of molecular histology, 2026, PMID 42185511): "Glycolysis was evaluated by measuring the extracellular acidification rate (ECAR), oxygen consumption rate (OCR), and levels of glucose, lactate, and adenosine triphosphate (ATP)."
• May β-Asarone, Tenuifolin, and YuanZhi Decoction Restore Cognitive Function and Modulate GRIN2B-Associated Autophagy in Alzheimer's Disease. (Neurochemical research, 2026, PMID 42171824): "All treatments improved cognitive function, attenuated hippocampal neuronal loss and tau pathology, and restored metabolic parameters (ATP, ROS, DT, SOD2)."
• May Aerobic Fermentation Strategy to Promote Nisin Production by Lactococcus lactis. (Journal of agricultural and food chemistry, 2026, PMID 42096270): "Aerobic cultivation of L. lactis CF6 significantly increased intracellular ATP and the NAD+/NADH ratio, thus redirecting metabolic flux toward nisin production."
• May Fe3+-ATP-CK cascade-regulated carbon dots fluorescent probe for dynamic monitoring of creatine kinase activity. (Talanta, 2026, PMID 41610527): "Conventional fluorescence detection often relies on ATP as an intermediate, where CK activity alters ATP levels to allow indirect CK measurement."
• May Nucleotide-Derived Competitive Inhibitors of Ectonucleotidase CD39─A Promising Extracellular Target for Immunotherapy of Cancer. (Journal of medicinal chemistry, 2026, PMID 42067197): "PSB-24379 reduced ATP hydrolysis in melanoma and breast cancer cell membranes and partially reverted ATP-mediated effects on T cell activation and proliferation in an ATP-rich environment."
• May RGFP966 inhibits activation of AIM2 inflammasomes to promote mitophagy to relieve acute gouty arthritis. (PloS one, 2026, PMID 42133647): "Furthermore, RGFP966 decreased the level of reactive oxygen species (ROS), increased the level of ATP and MMP, and promoted the levels of Pink1, Parkin and LC3-II."
• May Aggregation of Phosphates Enhances Enzyme Activity in Aqueous Solution. (Chemphyschem : a European journal of chemical physics and physical chemistry, 2026, PMID 42059824): "Diffusion coefficients and viscosities of tetrabutylammonium dihydrogen phosphate ([NBu4]+[H2PO4]-), potassium dihydrogen phosphate (K+[H2PO4]-), tetrabutylammonium bromide ([NBu4]+[Br]-), tetrabutylammonium chloride ([NBu4]+[Cl]-), and biologically relevant phosphate salts adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) were measured in aqueous solutions as a function of concentration across millimolar concentrations."