Lv HC, Fan YF, Ge XJ. Carnitine palmitoyltransferase 1A facilitates the senescence of human dental pulp stem cells by Parkin succinylation-mediated mitophagy. World J Stem Cells 2026; 18(9): 122036 [DOI: 10.4252/wjsc.122036]
Corresponding Author of This Article
Xue-Jun Ge, Shanxi Medical University School and Hospital of Stomatology, Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, No. 56 Xinjiannan Road, Yingze District, Taiyuan 030001, Shanxi Province, China. gxj19722003@163.com
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Dentistry, Oral Surgery & Medicine
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research-article
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Lv HC, Fan YF, Ge XJ. Carnitine palmitoyltransferase 1A facilitates the senescence of human dental pulp stem cells by Parkin succinylation-mediated mitophagy. World J Stem Cells 2026; 18(9): 122036 [DOI: 10.4252/wjsc.122036]
World J Stem Cells. Sep 26, 2026; 18(9): 122036 Published online Sep 26, 2026. doi: 10.4252/wjsc.122036
Carnitine palmitoyltransferase 1A facilitates the senescence of human dental pulp stem cells by Parkin succinylation-mediated mitophagy
Hai-Chi Lv, Yu-Feng Fan, Xue-Jun Ge
Hai-Chi Lv, Yu-Feng Fan, Xue-Jun Ge, Shanxi Medical University School and Hospital of Stomatology, Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan 030001, Shanxi Province, China
Author contributions: Lv HC contributed to investigation, formal analysis, visualization and roles/writing - original draft; Fan YF contributed to conceptualization, data curation, methodology and software; Ge XJ contributed to project administration, resources, supervision and validation, writing - review & editing. All authors have read and approved the final version to be published.
AI contribution statement: Portions of this manuscript were edited using AI tools for language refinement. The authors were responsible and agree to accountability for all scientific content.
Supported by Project Task Book for Shanxi Provincial Basic Research Program, No. 202303021211127.
Institutional animal care and use committee statement: The animal study was approved by the Experimental Animal Welfare Ethics Committee of Beijing MDKN (Approval No. MDKN-2024-270). All methods were carried out in accordance with relevant guidelines and regulations.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The raw data can be obtained on request from the corresponding author.
Corresponding author: Xue-Jun Ge, Shanxi Medical University School and Hospital of Stomatology, Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, No. 56 Xinjiannan Road, Yingze District, Taiyuan 030001, Shanxi Province, China. gxj19722003@163.com
Received: April 8, 2026 Revised: June 16, 2026 Accepted: September 18, 2026 Published online: September 26, 2026 Processing time: 169 Days and 23.5 Hours
Abstract
BACKGROUND
Senescence of human dental pulp stem cells (DPSCs) weakens the differentiation and regeneration ability, affecting their function and the tooth, and limiting their in vitro application. Carnitine palmitoyltransferase 1A (CPT1A) has been reported to regulate the aging of multiple cells.
AIM
To investigate the effects of CPT1A on DPSC senescence and the underlying mechanism, particularly PTEN-induced kinase 1-mediated mitophagy.
METHODS
Human DPSCs at seven (p7) and 15 (p15) passages were used for functional analysis. Cell senescence and mitophagy were evaluated using senescence associated β-galactosidase staining and immunoblotting. The effect of CPT1A on Parkin succinylation was assessed using co-immunoprecipitation (co-IP)/IP, immunoblotting, and cycloheximide chase experiment. The aging mouse model was established using D-galactose (D-gal), and both senescence and mitophagy were evaluated in dental pulp tissues.
RESULTS
CPT1A expression was increased in DPSCs at p15. Compared with p7 cells, p15 cells had higher senescence and lower mitophagy levels, while knockdown of CPT1A inhibited senescence and promoted mitophagy of p15 DPSCs. Additionally, silencing CPT1A reduced the succinylation of Parkin at K27 site and enhanced Parkin protein stability. CPT1A succinylates Parkin and suppresses mitophagy through its lysine succinyltransferase activity. Moreover, the mitophagy inhibitor Mdivi-1 or knockdown of Parkin abrogated the effects on senescence and mitophagy mediated by CPT1A knockdown. The in vivo experiments showed that silencing CPT1A inhibits D-gal-induced dental pulp aging by promoting Parkin-mediated mitophagy.
CONCLUSION
Silencing of CPT1A suppresses senescence of DPSCs by facilitating mitophagy, which is associated with the inhibition of succinylation of Parkin, suggesting a new mechanism and target for DPSC aging.
Core Tip: This study reveals that carnitine palmitoyltransferase 1A (CPT1A) promotes senescence of human dental pulp stem cells (DPSCs) by inhibiting Parkin-mediated mitophagy. CPT1A is upregulated in senescent late-passage DPSCs, and its knockdown suppresses senescence while enhancing mitophagy. Mechanistically, CPT1A acts as a succinyltransferase that succinylates Parkin protein at lysine 27, reducing Parkin stability. Silencing CPT1A decreases Parkin succinylation, stabilizes Parkin, and restores mitophagy. In vivo, CPT1A knockdown alleviates D galactose-induced dental pulp aging via Parkin-dependent mitophagy. This research identifies a novel CPT1A-Parkin succinylation axis controlling DPSC senescence.
