OSCR

ACLY alleviates cerebral ischemia/reperfusion injury by reducing oxidative stress and enhancing mitochondrial function via histone acetylation.

Overview

Authors: Xiaona Sun1,2,3, Rui Zhao1, Qidi Zhou1,2,3, Xiaorong Wang1,2,3, Yuxin Li1,2,3, Yongkun Yang4, Zhiyuan Zhao1, Yu Cui2,3, Rui Xu1,3
ORCID iDs: Yu Cui, Rui Xu
  1. Department of Interventional Radiology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266000 Shandong China
  2. China Uruguay Bio-nano Pharmaceutical Joint Laboratory, Qingdao University, Ningxia Road 308, Qingdao, 266071 Shandong China
  3. Qingdao Medical College, Qingdao University, Ningxia Road 308, Qingdao, 266071 Shandong China
  4. Department of Department of Neurosurgery, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266000 Shandong China
Institutions: Qingdao University (China); Affiliated Hospital of Qingdao University (China)
Journal: Cell death & disease, volume 17, issue 1, article 772
Dates: received 13 October 2025; accepted 12 June 2026; published online 22 June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41419-026-09021-4 · PMID 42331781 · PMCID PMC13538641 · OpenAlex W7165567683
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), stroke (population), cellular / molecular (subfield)
Methods: Statistics
Keywords: Stroke, Cellular neuroscience
MeSH: ATP Citrate (pro-S)-Lyase*, Brain Ischemia*, Histones*, Mitochondria*, Oxidative Stress*, Reperfusion Injury*, Acetylation, Animals, Epigenesis, Genetic, Infarction, Middle Cerebral Artery, Male, Mice, Mice, Inbred C57BL, Neurons (* major topic)
Topic: Neuroinflammation and Neurodegeneration Mechanisms (Neurology, Neuroscience), according to OpenAlex
Funding: National Natural Science Foundation of China (National Science Foundation of China) (32470984); Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation) (ZR202102190696)
Citations: not cited yet (Europe PMC); 53 references in the paper

Abstract

Cell metabolism and epigenetic regulation play crucial roles in modulating cerebral ischemia/reperfusion (I/R) injury. How cell metabolism regulates cerebral I/R injury by regulating epigenetic modifications remains unclear. In this study, we utilized an in vivo injury model of transient middle cerebral artery occlusion (tMCAO) in C57BL/6 mice. The middle cerebral artery was occluded for 90 min, followed by reperfusion at different time points. We observed that the expression of ATP-citrate lyase (ACLY), an important enzyme involved in lipid synthesis, was significantly upregulated under cerebral I/R conditions. Inhibition of ACLY markedly exacerbated cerebral I/R injury in vivo. ACLY inhibition and knockdown in vitro also reduced cell viability in cultured neurons following oxygen-glucose deprivation/reoxygenation (OGD/R). Mechanistic studies revealed that ACLY enhances histone acetylation at the promoter regions of mitochondrial respiratory chain complexes by facilitating the accumulation of acetyl-CoA, thereby improving mitochondrial function and attenuating oxidative stress. Our findings reveal a novel metabolic-epigenetic axis mediated by ACLY in the regulation of cerebral I/R injury which may serve as a potential target for therapeutic intervention in ischemic stroke.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

Data availability

The data generated or analyzed in this study are included in this published article. RNA-seq data has been deposited in the National Center for Biotechnology Information database under access code PRJNA1335777 (https://dataview.ncbi.nlm.nih.gov/object/PRJNA1335777).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 2 keywords, 14 MeSH terms, 2 funders, 51 references.

Cite

This paper

Sun, X., Zhao, R., Zhou, Q., Wang, X., Li, Y., Yang, Y., Zhao, Z., Cui, Y., & Xu, R. (2026). ACLY alleviates cerebral ischemia/reperfusion injury by reducing oxidative stress and enhancing mitochondrial function via histone acetylation. Cell death & disease, 17(1), 772. https://doi.org/10.1038/s41419-026-09021-4

BibTeX

@article{sun2026acly,
author = {Sun, Xiaona and Zhao, Rui and Zhou, Qidi and Wang, Xiaorong and Li, Yuxin and Yang, Yongkun and Zhao, Zhiyuan and Cui, Yu and Xu, Rui},
title = {{ACLY alleviates cerebral ischemia/reperfusion injury by reducing oxidative stress and enhancing mitochondrial function via histone acetylation}},
journal = {Cell death \& disease},
year = {2026},
month = jun,
volume = {17},
number = {1},
pages = {772},
publisher = {Nature Publishing Group},
issn = {2041-4889},
doi = {10.1038/s41419-026-09021-4},
url = {https://doi.org/10.1038/s41419-026-09021-4},
pmid = {42331781},
pmcid = {PMC13538641}
}

RIS

TY - JOUR
AU - Sun, Xiaona
AU - Zhao, Rui
AU - Zhou, Qidi
AU - Wang, Xiaorong
AU - Li, Yuxin
AU - Yang, Yongkun
AU - Zhao, Zhiyuan
AU - Cui, Yu
AU - Xu, Rui
TI - ACLY alleviates cerebral ischemia/reperfusion injury by reducing oxidative stress and enhancing mitochondrial function via histone acetylation
T2 - Cell death & disease
J2 - Cell Death Dis
PY - 2026
DA - 2026/06/22
VL - 17
IS - 1
SP - 772
SN - 2041-4889
PB - Nature Publishing Group
DO - 10.1038/s41419-026-09021-4
UR - https://doi.org/10.1038/s41419-026-09021-4
LA - en
ER -

CSL-JSON

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