The role of mitochondrial dynamics in cerebral ischemia-reperfusion injury

Huang, Jie; Chen, Lei; Yao, Zi-Meng; Sun, Xiao‐Rong; Tong, Xuhui; Dong, Shuying

doi:10.1016/j.biopha.2023.114671

Cited by 26 publications

(9 citation statements)

References 119 publications

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“…The results indicated that Mito-IQS showed negligible cytotoxicity to SH-SY5Y cells at a high concentration of 15 μM (Figure S20). Increasing evidence has indicated that brain cells undergo severe damage during CIRI, which results in an imbalance of mitochondrial redox reactions and influences mitochondrial energy production. − The interaction of these factors results in mitochondrial dysfunction, subsequently causing alterations in mitochondrial viscosity and H 2 O 2 levels. , Therefore, studying the mitochondrial viscosity and H 2 O 2 during CIRI is crucial. Mito-IQS was further employed to simultaneously image viscosity and H 2 O 2 in the mitochondria (Figure A).…”

Section: Resultsmentioning

confidence: 99%

Fluorescent Probe for Investigating the Mitochondrial Viscosity and Hydrogen Peroxide Changes in Cerebral Ischemia/Reperfusion Injury

Fang,

Deng,

Zhao

et al. 2024

Anal. Chem.

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Cerebral ischemia−reperfusion injury (CIRI), a cause of cerebral dysfunction during cerebral infarction treatment, is closely associated with mitochondrial viscosity and hydrogen peroxide (H 2 O 2 ). However, the accurate measurement of mitochondrial viscosity and H 2 O 2 levels in CIRI is challenging because of the lack of sufficient selectivity and blood−brain barrier (BBB) penetration of existing monitoring tools related to CIRI, hampering the exploration of the role of mitochondrial viscosity and H 2 O 2 in CIRI. To address this issue, we designed an activatable fluorescent probe, mitochondria-targeting styryl-quinolin-ium (Mito-IQS), with excellent properties including high selectivity, mitochondrial targeting, and BBB penetration, for the visualization of mitochondrial viscosity and H 2 O 2 in the brain. Based on the real-time monitoring capabilities of the probe, bursts of mitochondrial viscosity and H 2 O 2 levels were visualized during CIRI. This probe can be used to monitor the therapeutic effects of butylphthalein treatment. More importantly, in vivo experiments further confirmed that CIRI was closely associated with the mitochondrial viscosity and H 2 O 2 levels. This discovery provides new insights and tools for the study of CIRI and is expected to accelerate the process of CIRI diagnosis, treatment, and drug design.

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Section: Resultsmentioning

confidence: 99%

Fluorescent Probe for Investigating the Mitochondrial Viscosity and Hydrogen Peroxide Changes in Cerebral Ischemia/Reperfusion Injury

Fang,

Deng,

Zhao

et al. 2024

Anal. Chem.

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“…Neurodegenerative diseases constitute a spectrum of complex heterogeneous disorders characterized by the progressive death of nerve cells and loss of brain tissues, 157,158 and their treatments are limited. Given that nerve cells require high levels of mitochondrial metabolism for their functions, mitochondrial dysfunction has emerged as one of the predominant phenotypes in neurodegenerative diseases 12,159,160,69 . Excessive mitochondrial fission, downregulation of mitochondrial fusion, as well as a reduction in mitophagy, are observed in neurodegenerative disorders with diverse genetic and environmental causes supported by several lines of clinical evidence, 12 including Charcot–Marie–Tooth disease (CMT) type 2A (CMT2A), 161,162 dominant optic atrophy (DOA), 163 Parkinson's disease (PD), 164 Huntington's diseases (HD), 165 Alzheimer's disease (AD), 166 and amyotrophic lateral sclerosis (ALS), 167 which have various pathophysiological etiology 168 .…”

Section: Mitochondrial Dynamics and Diseasementioning

confidence: 99%

The role of mitochondrial dynamics in disease

Wang,

Dai,

et al. 2023

MedComm

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Mitochondria are multifaceted and dynamic organelles regulating various important cellular processes from signal transduction to determining cell fate. As dynamic properties of mitochondria, fusion and fission accompanied with mitophagy, undergo constant changes in number and morphology to sustain mitochondrial homeostasis in response to cell context changes. Thus, the dysregulation of mitochondrial dynamics and mitophagy is unsurprisingly related with various diseases, but the unclear underlying mechanism hinders their clinical application. In this review, we summarize the recent developments in the molecular mechanism of mitochondrial dynamics and mitophagy, particularly the different roles of key components in mitochondrial dynamics in different context. We also summarize the roles of mitochondrial dynamics and target treatment in diseases related to the cardiovascular system, nervous system, respiratory system, and tumor cell metabolism demanding high‐energy. In these diseases, it is common that excessive mitochondrial fission is dominant and accompanied by impaired fusion and mitophagy. But there have been many conflicting findings about them recently, which are specifically highlighted in this view. We look forward that these findings will help broaden our understanding of the roles of the mitochondrial dynamics in diseases and will be beneficial to the discovery of novel selective therapeutic targets.

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“…Most strategies for mitochondrial dynamics focus on inhibiting mitochondrial fission or promoting mitochondrial fusion. 11 Therefore, regulating mitochondrial dynamics is essential for maintaining mitochondrial homeostasis to mitigate CIRI and promote neurological function recovery in patients with ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV combined with ligustrazine ameliorates abnormal mitochondrial dynamics via Drp1 SUMO/deSUMOylation in cerebral ischemia–reperfusion injury

Chen,

Yang,

Zhou

et al. 2024

CNS Neurosci Ther

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ObjectivesAstragaloside IV (AST IV) and ligustrazine (Lig), the main ingredients of Astragali Radix and Chuanxiong Rhizoma respectively, have demonstrated significant benefits in treatment of cerebral ischemia ‐reperfusion injury (CIRI); however, the mechanisms underlying its benificial effects remain unclear. SUMO‐1ylation and deSUMO‐2/3ylation of dynamin‐related protein 1 (Drp1) results in mitochondrial homeostasis imbalance following CIRI, which subsequently aggravates cell damage. This study investigates the mechanisms by which AST IV combined with Lig protects against CIRI, focusing on the involvement of SUMOylation in mitochondrial dynamics.MethodsRats were administrated AST IV and Lig for 7 days, and middle cerebral artery occlusion was established to mimic CIRI. Neural function, cerebral infarction volume, cerebral blood flow, cognitive function, cortical pathological lesions, and mitochondrial morphology were measured. SH‐SY5Y cells were subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) injury. Mitochondrial membrane potential and lactic dehydrogenase (LDH), reactive oxygen species (ROS), and adenosine triphosphate (ATP) levels were assessed with commercial kits. Moreover, co‐immunoprecipitation (Co‐IP) was used to detect the binding of SUMO1 and SUMO2/3 to Drp1. The protein expressions of Drp1, Fis1, MFF, OPA1, Mfn1, Mfn2, SUMO1, SUMO2/3, SENP1, SENP2, SENP3, SENP5, and SENP6 were measured using western blot.ResultsIn rats with CIRI, AST IV and Lig improved neurological and cognitive functions, restored CBF, reduced brain infarct volume, and alleviated cortical neuron and mitochondrial damage. Moreover, in SH‐SY5Y cells, the combination of AST IV and Lig enhanced cellular viability, decreased release of LDH and ROS, increased ATP content, and improved mitochondrial membrane potential. Furthermore, AST IV combined with Lig reduced the binding of Drp1 with SUMO1, increased the binding of Drp1 with SUMO2/3, suppressed the expressions of Drp1, Fis1, MFF, and SENP3, and increased the expressions of OPA1, Mfn1, Mfn2, SENP1, SENP2, and SENP5. SUMO1 overexpression promoted mitochondrial fission and inhibited mitochondrial fusion, whereas SUMO2/3 overexpression suppressed mitochondrial fission. AST IV combined with Lig could reverse the effects of SUMO1 overexpression while enhancing those of SUMO2/3 overexpression.ConclusionsThis study posits that the combination of AST IV and Lig has the potential to reduce the SUMO‐1ylation of Drp1, augment the SUMO‐2/3ylation of Drp1, and thereby exert a protective effect against CIRI.

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The role of mitochondrial dynamics in cerebral ischemia-reperfusion injury

Cited by 26 publications

References 119 publications

Fluorescent Probe for Investigating the Mitochondrial Viscosity and Hydrogen Peroxide Changes in Cerebral Ischemia/Reperfusion Injury

Fluorescent Probe for Investigating the Mitochondrial Viscosity and Hydrogen Peroxide Changes in Cerebral Ischemia/Reperfusion Injury

The role of mitochondrial dynamics in disease

Astragaloside IV combined with ligustrazine ameliorates abnormal mitochondrial dynamics via Drp1 SUMO/deSUMOylation in cerebral ischemia–reperfusion injury

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