Tools
Tools
Xu, Jiacheng, Sun, Lujia, Chen, Miaomiao, Chao, Bingdi, He, Jie, Liu, Hongli, Huang, Dongni, Wang, Jie, Xie, Lumei, Baker, Philip N. 
ORCID: https://orcid.org/0000-0002-4592-6427, Ding, Yubin, Qi, Hongbo and Luo, Xin
(2026)
Elevated BACH1 Contributes to Mitochondrial Succinylome Remodeling and Trophoblast Bioenergetic Dysfunction in Preeclampsia.
Antioxidants, 15 (7).
ISSN 2076-3921
Preview |
PDF (antioxidants-15-00835)
- Published Version
Available under License Creative Commons Attribution. Download (21MB) | Preview |
Abstract
Preeclampsia (PE) is a major pregnancy complication characterized by placental dysfunction and metabolic disturbances. Although mitochondrial abnormalities are frequently observed in PE, the upstream regulatory mechanisms remain incompletely understood. Here, we investigated the potential involvement of BACH1 in trophoblast dysfunction in PE and explored its association with mitochondrial metabolic alterations and protein succinylation. BACH1 expression was assessed in placental tissues and plasma samples from patients with PE, its functional effects were examined in trophoblast cell lines and BACH1 overexpression mouse models, and metabolic, bioenergetic, and succinylation-related alterations were evaluated using multi-omics and functional analyses. BACH1 expression was elevated in PE placentas and correlated with disease severity. In trophoblasts, BACH1 overexpression impaired proliferation, invasion, and trophoblast-mediated angiogenesis and was accompanied by mitochondrial and metabolic abnormalities, while quantitative succinylproteomic analysis revealed widespread alterations in mitochondrial protein succinylation. In vivo, BACH1 overexpression induced key PE-like features, including hypertension, fetal growth restriction, and placental abnormalities, and glycine supplementation partially rescued the trophoblast dysfunction associated with BACH1 overexpression. Together, evidence from clinical samples and experimental models suggests that BACH1 is associated with mitochondrial succinylation remodeling and trophoblast dysfunction in PE, supporting the hypothesis that BACH1-associated metabolic dysregulation and mitochondrial succinylation remodeling may contribute to PE pathogenesis. Further studies are required to establish the causal relevance and clinical significance of these mechanisms in human PE.
| Item Type: | Article |
|---|---|
| Additional Information: | Data Availability Statement: The mass spectrometry datasets generated in this study have been deposited in the OMIX, China National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences [53,54] (accession numbers OMIX015392 for metabolomics and OMIX015360 for succinyllysine proteomics). They are publicly accessible through the OMIX repository (https://ngdc.cncb.ac.cn/omix, accessed on 3 March 2026). Additionally, the datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. |
| Uncontrolled Keywords: | bach1,lysine succinylation,mitochondrial metabolism,preeclampsia,trophoblast,food science,physiology,biochemistry,molecular biology,clinical biochemistry,cell biology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1100/1106 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 25 Aug 2026 15:20 |
| Last Modified: | 30 Aug 2026 23:03 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/104344 |
| DOI: | 10.3390/antiox15070835 |
Downloads
Downloads per month over past year
Actions (login required)
 |
View Item |