World J Transl Med. Nov 28, 2026; 12(4): 125988 Published online Nov 28, 2026. doi: 10.5528/wjtm.125988
Adenosine triphosphate homeostasis in cardiovascular cell-fate transitions: Adenosine triphosphate-induced cellular senescence and adenosine triphosphate-induced cell death
Rui Zhao, Jing-Jing Zhang, Siti Nurfatimah Mohd Shahpudin, Mohammad Syamsul Reza Harun, Hao-Ling Zhang, Sandai Doblin
Rui Zhao, Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
Jing-Jing Zhang, Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, Affiliated Cardiovascular Hospital of Kunming Medical University, Yunnan Provincial Cardiovascular Clinical Medical Center, Yunnan Provincial Cardiovascular Clinical Medical Research Center, Kunming 650000, Yunnan Province, China
Siti Nurfatimah Mohd Shahpudin, Mohammad Syamsul Reza Harun, Hao-Ling Zhang, Sandai Doblin, Department of Biomedical Sciences, Pusat Kanser Tun Abdullah Ahmad Badawi, Universiti Sains Malaysia, Kepala Batas 13200, Pulau Pinang, Malaysia
Co-corresponding authors: Hao-Ling Zhang and Sandai Doblin.
Author contributions: Zhao R and Zhang JJ conducted the literature search, organized the relevant literature, and drafted the manuscript; Shahpudin SNM and Harun MSR contributed to literature verification and manuscript revision; Zhang HL and Doblin S conceived and designed the review, supervised the work, and critically revised the manuscript; and all authors read and approved the final manuscript. Zhang HL contributed substantially to the conceptual framework, scientific organization, evidence interpretation, and manuscript revision. Doblin S provided overall scientific supervision, refined the central concepts, critically evaluated the evidence, and guided manuscript revision. Zhang HL and Doblin S jointly supervised the scientific development of the review and shared responsibility for its conceptual framework, evidence interpretation, and final revision. Their complementary contributions support their roles as co-corresponding authors.
AI contribution statement: No AI tool was used to generate research data, interpret results, or formulate conclusions. All authors have verified the accuracy, originality, references, and integrity of the final manuscript and accept full responsibility for its content.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
Corresponding author: Sandai Doblin, Department of Biomedical Sciences, Pusat Kanser Tun Abdullah Ahmad Badawi, Universiti Sains Malaysia, Kepala Batas 13200, Pulau Pinang, Malaysia. doblin@usm.my
Received: July 22, 2026 Revised: August 27, 2026 Accepted: October 9, 2026 Published online: November 28, 2026 Processing time: 105 Days and 20.9 Hours
Abstract
This narrative review examines adenosine triphosphate (ATP) homeostasis as a context-dependent framework linking cellular energy metabolism, stress responses, and cell-fate regulation in the cardiovascular system. Intracellular ATP is closely related to mitochondrial oxidative phosphorylation, glycolysis, and cellular energy demand, whereas extracellular ATP serves as an important signal in purinergic communication. Changes in ATP production, utilization, release, and clearance may therefore influence how cardiovascular cells respond to metabolic and pathological stress. When these changes persist, they may be associated with senescence-related alterations or, under more severe conditions, with irreversible cell injury and death. In this review, ATP-induced cellular senescence and ATP-induced cell death are used to describe these ATP-associated cell-fate changes. They are not intended to replace established mechanisms of cellular senescence or regulated cell death. Current evidence is predominantly preclinical and heterogeneous across experimental models, cell types, ATP compartments, and disease contexts, and a defined ATP threshold separating adaptation, senescence, and cell death has not been established. The biological consequences of ATP disturbance are likely to depend on ATP compartment, cell type, disease stage, and the intensity and duration of stress. Further studies that directly measure ATP together with mitochondrial function and cell-fate changes will be important for determining the role of ATP homeostasis in cardiovascular disease.
Core Tip: Adenosine triphosphate (ATP) homeostasis provides an integrative framework for understanding cardiovascular cell-fate transitions by linking energy metabolism, mitochondrial function, and purinergic signaling. By distinguishing intracellular bioenergetic ATP from extracellular purinergic ATP, this review examines how ATP production, utilization, release, and clearance may shape cellular responses from reversible adaptation to senescence-associated phenotypes and regulated cell death. ATP-induced cellular senescence and ATP-induced cell death are used to describe ATP-associated cell-fate changes rather than distinct biological categories. This perspective highlights compartment-specific ATP regulation as an important area for clarifying cardiovascular disease mechanisms and for evaluating the potential translational relevance of ATP-associated metabolic regulation.
