FUNDC1 Mediated Mitophagy in Epileptic Hippocampal Neuronal Injury Induced by Magnesium-Free Fluid

Zhang, Yinna; Lian, Yajun; Lian, Xiaolei; Zhang, Haifeng; Chen, Yuan; Sheng, Hanqing; Feng, Rui

doi:10.1007/s11064-022-03749-z

Cited by 12 publications

(4 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mitochondrial membrane proteins such as Nip3-like protein X (Nix) can also be involved in Parkin-dependent mitochondrial autophagy [37]. FUN14 domain-containing protein 1 (FUNDC1) receptor [38] and Bcl-2-like protein 13 (Bcl-2-like protein 13, BCL2L13) [39] induce mitochondrial autophagy in a Parkin non-dependent manner, whether these regulatory mitochondrial pathways are involved in the development of lung injury in heat stroke still needs to be further explored.…”

Section: Discussionmentioning

confidence: 99%

Activation of Pink1/Parkin-mediated mitochondrial autophagy alleviates exertional heat stroke-induced acute lung injury in rats

Wang,

Sun,

Jiang

et al. 2024

View full text Add to dashboard Cite

OBJECTIVE: To investigate the role of Pink1/Parkin-mediated mitochondrial autophagy in exertional heat stroke-induced acute lung injury in rats. METHODS: Sixty SD rats were divided into four groups: normal group (CON group), normal Parkin overexpression group (CON + Parkin group), exertional heat stroke group (EHS group), and exertional heat stroke Parkin overexpression group (EHS + Parkin group). Adeno-associated virus carrying the Parkin gene was intravenously injected into the rats to overexpress Parkin in the lung tissue. An exertional heat stroke rat model was established, and survival curves were plotted. Lung micro-CT was performed, and lung coefficient and pulmonary microvascular permeability were measured. RESULTS: Compared with the EHS group, the survival rate of rats in the EHS + Parkin overexpression group was significantly increased, lung coefficient and pulmonary microvascular permeability were reduced, and pathological changes such as exudation and consolidation were significantly reduced. The levels of inflammatory factors IL-6, IL-1β, TNF- α, and ROS were significantly decreased; the degree of mitochondrial swelling in type II alveolar epithelial cells was reduced, and no vacuolization was observed. Lung tissue apoptosis was reduced, and the colocalization fluorescence of Pink1 and Parkin, as well as LC3 and Tom20, were increased. The expression of Parkin and LC3-II/LC3-I ratio in lung tissue were both increased, while the expression of P62, Pink1, MFN2, and PTEN-L was decreased. CONCLUSION: Impairment of Pink1/Parkin-mediated mitochondrial autophagy function is one of the mechanisms of exertional heat stroke-induced acute lung injury in rats. Activation of the Pink1/Parkin pathway can alleviate acute lung injury caused by exertional heat stroke.

show abstract

Section: Discussionmentioning

confidence: 99%

Activation of Pink1/Parkin-mediated mitochondrial autophagy alleviates exertional heat stroke-induced acute lung injury in rats

Wang,

Sun,

Jiang

et al. 2024

View full text Add to dashboard Cite

show abstract

“…It has been discovered that, in cerebral ischaemia-reperfusion injury, FUNDC1could suppress the neuronal apoptosis and improve mitochondrial function [ 48 ]. Under non-hypoxic conditions, such as the diabetic CI and the epileptic neuronal injury, FUNDC1 was observed to protect neurons from damage by enhancing mitosis and neuronal viability and attenuating neuronal apoptosis [ 49 , 50 ]. These previous data suggested thatFUNDC1played a neuronal protective role under both hypoxic and non-hypoxic conditions.…”

Section: Discussionmentioning

confidence: 99%

NTRK1 knockdown induces mouse cognitive impairment and hippocampal neuronal damage through mitophagy suppression via inactivating the AMPK/ULK1/FUNDC1 pathway

Yang,

Wu,

et al. 2023

Cell Death Discov.

View full text Add to dashboard Cite

Hippocampal neuronal damage may induce cognitive impairment. Neurotrophic tyrosine kinase receptor 1 (NTRK1) reportedly regulates neuronal damage, although the underlying mechanism remains unclear. The present study aimed to investigate the role of NTRK1 in mouse hippocampal neuronal damage and the specific mechanism. A mouse NTRK1-knockdown model was established and subjected to pre-treatment with BAY-3827, followed by a behavioral test, Nissl staining, and NeuN immunofluorescence (IF) staining to evaluate the cognitive impairment and hippocampal neuronal damage. Next, an in vitro analysis was conducted using the CCK-8 assay, TUNEL assay, NeuN IF staining, DCFH-DA staining, JC-1 staining, ATP content test, mRFP-eGFP-LC3 assay, and LC3-II IF staining to elucidate the effect of NTRK1 on mouse hippocampal neuronal activity, apoptosis, damage, mitochondrial function, and autophagy. Subsequently, rescue experiments were performed by subjecting the NTRK1-knockdown neurons to pre-treatment with O304 and Rapamycin. The AMPK/ULK1/FUNDC1 pathway activity and mitophagy were detected using western blotting (WB) analysis. Resultantly, in vivo analysis revealed that NTRK1 knockdown induced mouse cognitive impairment and hippocampal tissue damage, in addition to inactivating the AMPK/ULK1/FUNDC1 pathway activity and mitophagy in the hippocampal tissues of mice. The treatment with BAY-3827 exacerbated the mouse depressive-like behavior induced by NTRK1 knockdown. The results of in vitro analysis indicated that NTRK1 knockdown attenuated viability, NeuN expression, ATP production, mitochondrial membrane potential, and mitophagy, while enhancing apoptosis and ROS production in mouse hippocampal neurons. Conversely, pre-treatment with O304 and rapamycin abrogated the suppression of mitophagy and the promotion of neuronal damage induced upon NTRK1 silencing. Conclusively, NTRK1 knockdown induces mouse hippocampal neuronal damage through the suppression of mitophagy via inactivating the AMPK/ULK1/FUNDC1 pathway. This finding would provide insight leading to the development of novel strategies for the treatment of cognitive impairment induced due to hippocampal neuronal damage.

show abstract

“…FUNDC1 is reported to play an important role in several diseases, such as cancer, cardiovascular disease, and neurological disorders, including AD ( Chen et al, 2016 ). In an in vitro model of hippocampal neurons obtained from acquired epilepsy, low FUNDC1 expression significantly increased neuronal apoptosis ( Zhang et al, 2023 ). The downregulation of FUNDC1 levels in cases of AD in particular may lead to mitochondrial dysfunction, accelerating the AD progression ( Jetto et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of mitochondrial-related genes as potential biomarkers for the subtyping and prediction of Alzheimer’s disease

Zhang

et al. 2023

Front. Mol. Neurosci.

View full text Add to dashboard Cite

IntroductionAlzheimer’s disease (AD) is a progressive and debilitating neurodegenerative disorder prevalent among older adults. Although AD symptoms can be managed through certain treatments, advancing the understanding of underlying disease mechanisms and developing effective therapies is critical.MethodsIn this study, we systematically analyzed transcriptome data from temporal lobes of healthy individuals and patients with AD to investigate the relationship between AD and mitochondrial autophagy. Machine learning algorithms were used to identify six genes—FUNDC1, MAP1LC3A, CSNK2A1, VDAC1, CSNK2B, and ATG5—for the construction of an AD prediction model. Furthermore, AD was categorized into three subtypes through consensus clustering analysis.ResultsThe identified genes are closely linked to the onset and progression of AD and can serve as reliable biomarkers. The differences in gene expression, clinical features, immune infiltration, and pathway enrichment were examined among the three AD subtypes. Potential drugs for the treatment of each subtype were also identified.DiscussionThe findings observed in the present study can help to deepen the understanding of the underlying disease mechanisms of AD and enable the development of precision medicine and personalized treatment approaches.

show abstract

FUNDC1 Mediated Mitophagy in Epileptic Hippocampal Neuronal Injury Induced by Magnesium-Free Fluid

Cited by 12 publications

References 53 publications

Activation of Pink1/Parkin-mediated mitochondrial autophagy alleviates exertional heat stroke-induced acute lung injury in rats

Activation of Pink1/Parkin-mediated mitochondrial autophagy alleviates exertional heat stroke-induced acute lung injury in rats

NTRK1 knockdown induces mouse cognitive impairment and hippocampal neuronal damage through mitophagy suppression via inactivating the AMPK/ULK1/FUNDC1 pathway

Identification of mitochondrial-related genes as potential biomarkers for the subtyping and prediction of Alzheimer’s disease

Contact Info

Product

Resources

About