A unified framework of cell death: Energy interdependence and multimodal interactions in disease pathogenesis-ZENTIME PUBLISHING CORPORATION LIMITED

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A unified framework of cell death: Energy interdependence and multimodal interactions in disease pathogenesis

Qilu Yan^1,*, Haoling Zhang^2,*, Ting Hu^3,4,#, Wangzheqi Zhang^4,#

¹Cancer Center, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, Hubei, China. ²Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang 13200, Malaysia. ³940th Hospital of PLA Joint Logistic Support Force, 333 Nanbinhe Road, Lanzhou 730050, Gansu, China. ⁴Naval Medical University, 800 Xiangyin Road, Shanghai 200433, China.

^*The authors contribute equally.

^#Co-corresponding authors.

Address correspondence to: Ting Hu, 940th Hospital of PLA Joint Logistic Support Force, 333 Nanbinhe Road, Lanzhou 730050, Gansu, China. E-mail: huting@smmu.edu.cn. Wangzheqi Zhang, Naval Medical University, 800 Xiangyin Road, Shanghai 200433, China. E-mail: zwzq001031@smmu.edu.cn.

DOI: https://doi.org/10.61189/159279rpqbrp

Received November 19, 2025; Accepted November 24, 2025; Published December 3, 2025

Abstract

There are various cell death programs that require energy metabolism, redox balance, and the mitochondria–endoplasmic reticulum stress axis. These programs do not operate in isolation; they respond to microenvironmental changes. This review summarizes their networked organization and discusses how Adenosine Triphosphate balance, mitochondrial dynamics, and redox control shape death decisions. The paper also discusses how inflammatory signals integrate diverse modes of death, the diagnostic information contained in cross-death biomarkers, and why multi-target approaches are better suited to complex diseases.

Keywords: Cell death, energy metabolism, redox regulation, mitochondria–endoplasmic reticulum stress, multitarget interventions