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The Role of Astrocytic Mitochondria in the Pathogenesis of Brain Ischemia

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Abstract

The morbidity rate of ischemic stroke is increasing annually with the growing aging population in China. Astrocytes are ubiquitous glial cells in the brain and play a crucial role in supporting neuronal function and metabolism. Increasing evidence shows that the impairment or loss of astrocytes contributes to neuronal dysfunction during cerebral ischemic injury. The mitochondrion is increasingly recognized as a key player in regulating astrocyte function. Changes in astrocytic mitochondrial function appear to be closely linked to the homeostasis imbalance defects in glutamate metabolism, Ca2+ regulation, fatty acid metabolism, reactive oxygen species, inflammation, and copper regulation. Here, we discuss the role of astrocytic mitochondria in the pathogenesis of brain ischemic injury and their potential as a therapeutic target.

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Abbreviations

AGCs:

Aspartate/glutamate carriers

ASC:

Apoptosis-associated speck-like protein containing a CARD

ApoE:

Apolipoproteins

Ca2+ :

Calcium

Cx43:

Connexin 43

Cu:

Copper

EAAC1:

Excitatory amino acid carrier 1

EAATs:

Excitatory amino acid transporters

ER:

Endoplasmic reticulum

FAO:

Mitochondrial fatty acid oxidation

FAs:

Fatty acids

GC:

Glutamate carriers

GCL:

Glutamate cysteine ligase

GDH:

Glutamate dehydrogenase

GLP:

Glucagon-like peptide

GJA1-20K:

20-kilodalton isoform

GS:

Glutamine synthetase

GSH:

Glutathione

HADHA:

Hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase

IP3R:

Inositol 1,4,5-trisphosphate receptor

IL-1β:

Interleukin-1β

IL-18:

Interleukin-18

α-KG:

α-ketoglutarate

KO:

Knockout

LDs:

Lipid droplets

MCU:

Mitochondrial calcium uniporter

MICU:

Mitochondrial calcium uptake

Miro-1:

Mitochondrial Rho-GTPase 1

mPTP:

Mitochondrial permeability transition pore

mtDNA:

Mitochondria DNA

NCLX:

Mitochondrial Na+/Ca2+ exchanger

NLRP3:

Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3

Nrf2:

Nuclear erythroid 2-related factor 2

OGD:

Oxygen-glucose deprivation

O–GlcNAc:

O-linked N-acetylglucosamine

PGC-1α:

Peroxisome proliferator-activated receptor gamma coactivator-1α

ROS:

Reactive oxygen species

SDH:

Succinate dehydrogenase

TCA:

Tricarboxylic acid

T3:

3,3,5 Triiodo-L-thyronine

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81971228) and the Natural Science Foundation of Hebei Province (Nos. H2021206160 and H2022206579).

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  1. Department of Pathophysiology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, Hebei, People’s Republic of China

    Ling-Yan Zhang, Yu-Yan Hu, Xi-Yun Liu, Xiao-Yu Wang, Shi-Chao Li, Jing-Ge Zhang, Xiao-Hui Xian, Wen-Bin Li & Min Zhang

  2. Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Shijiazhuang, 050017, People’s Republic of China

    Ling-Yan Zhang, Yu-Yan Hu, Jing-Ge Zhang, Xiao-Hui Xian, Wen-Bin Li & Min Zhang

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Contributions

L-YZ wrote the manuscript; X-YL, X-YW, and S-CL collected literatures; Y-YH drew the figure; Y-YH, J-GZ, X-HX, and W-BL reviewed and revised the manuscript; MZ designed and revised the manuscript.

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Correspondence to Min Zhang.

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Zhang, LY., Hu, YY., Liu, XY. et al. The Role of Astrocytic Mitochondria in the Pathogenesis of Brain Ischemia. Mol Neurobiol 61, 2270–2282 (2024). https://doi.org/10.1007/s12035-023-03714-z

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