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REVIEW ARTICLE

Morphological changes in intracellular small organelles during paraptosis and their relationship with diseases: A review

Huali Zhang1† ,  Xiang Cui1† ,  Fang Zhang1 ,  Min Cui1*
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1 Department Rehabilitation Medicine, Guilin Medical University Affiliated Hospital, Guilin, Guangxi, China
†These authors contributed equally to this work.
EJMO, 025040020 https://doi.org/10.36922/EJMO025040020
Submitted: 22 January 2025 | Revised: 6 March 2025 | Accepted: 31 March 2025 | Published: 25 April 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Paraptosis, a distinct form of programmed cell death, has attracted significant attention in cell biology due to its unique characteristics and potential therapeutic implications. Unlike classical apoptosis or necrosis, paraptosis is induced by specific stimuli and is marked by cell swelling, organelle distension, and the absence of nuclear condensation. This review explores the morphological changes in intracellular small organelles during paraptosis, including mitochondria, endoplasmic reticulum (ER), Golgi apparatus, lysosomes, and autophagosomes. Mitochondria undergo swelling and cristae loss, which impair adenosine triphosphate production and disrupt calcium homeostasis. The ER expands and experiences calcium ion imbalance, triggering ER stress and the unfolded protein response. The Golgi apparatus undergoes vasicularization and structural disassembly, impacting protein glycosylation and secretion. Lysosomal membrane instability leads to the release of acidic hydrolases, exacerbating cellular damage, while autophagosome formation is characterized by the development of double-membrane vesicles and their fusion with lysosomes. These organelle-specific changes are tightly regulated by complex intracellular signaling pathways and provide valuable insights into the mechanisms underlying paraptosis. Understanding these processes offers a theoretical foundation for developing novel therapeutic strategies targeting diseases characterized by dysregulated cell death. In tumor therapy, paraptosis, as a form of immunogenic cell death, can overcome tumor cell resistance to traditional apoptosis-inducing drugs and enhance the efficacy of immunotherapy. In neurodegenerative diseases, mild paraptosis is linked to tumorigenesis, whereas severe paraptosis is associated with neurodegenerative diseases such as Alzheimer’s disease. The mechanisms of action and potential therapeutic value of paraptosis in these disease contexts continue to be actively investigated.

Keywords
Paraptosis
Organelle morphological changes
Endoplasmic reticulum stress
Golgi apparatus dysfunction
Intracellular signaling pathways
Tumor therapy
Diseases
Funding
This work was supported by the Guangxi Natural Science Foundation of China (2025GXNSFHA069100, 2021GXNSFBA220005), and the Project for Enhancing the Research Capabilities of Young and Middle-Aged Teachers in Guangxi Colleges (No. 2024KY0517). Min Cui was supported by the Guangxi Medical and Health Key Cultivation Discipline Construction Project.
Conflict of interest
The authors declare no conflicts of interest.
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