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.