Mitophagy alleviates ischemia/reperfusion-induced microvascular damage through improving mitochondrial quality control

Wu, Dan; Ji, Haizhe; Du, Wenjuan; Ren, Lei; Qian, Geng

doi:10.1080/21655979.2022.2027065

Cited by 16 publications

(12 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In amino acid metabolic pathways, homocysteine is an intermediate amino acid that is metabolized from methionine to cysteine and has been shown to be associated with oxidative stress and endothelial damage [ 27 ]. Glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GPX) are major antioxidant molecules in ECs [ 28 ]. A recent report showed that brain ECs directly absorb and metabolize glutamate and utilize the resulting α-ketoglutarate in the tricarboxylic acid cycle, ultimately producing ATP in the absence of glucose [ 29 ].…”

Section: Resultsmentioning

confidence: 99%

Uncovering the Gene Regulatory Network of Endothelial Cells in Mouse Duchenne Muscular Dystrophy: Insights from Single-Nuclei RNA Sequencing Analysis

Shen

Kim

Hamrick

et al. 2023

Biology

View full text Add to dashboard Cite

Introduction: Duchenne muscular dystrophy (DMD) is a severe X-linked recessive disorder caused by mutations in the dystrophin gene, which leads to heart and respiratory failure. Despite the critical impact of DMD on endothelial cells (ECs), there is limited understanding of its effect on the endothelial gene network. The aim of this study was to investigate the impact of DMD on the gene regulatory network of ECs. Methods and Results: To gain insights into the role of the dystrophin muscular dystrophy gene (DMD) in ECs from Duchenne muscular dystrophy; the study utilized single-nuclei RNA sequencing (snRNA-seq) to evaluate the transcriptomic profile of ECs from skeletal muscles in DMD mutant mice (DMDmut) and wild-type control mice. The analysis showed that the DMD mutation resulted in the suppression of several genes, including SPTBN1 and the upregulation of multiple long noncoding RNAs (lncRNAs). GM48099, GM19951, and GM15564 were consistently upregulated in ECs and skeletal muscle cells from DMDmut, indicating that these dysregulated lncRNAs are conserved across different cell types. Gene ontology (GO) enrichment analysis revealed that the DMD mutation activated the following four pathways in ECs: fibrillary collagen trimer, banded collagen fibril, complex of collagen trimers, and purine nucleotide metabolism. The study also found that the metabolic pathway activity of ECs was altered. Oxidative phosphorylation (OXPHOS), fatty acid degradation, glycolysis, and pyruvate metabolism were decreased while purine metabolism, pyrimidine metabolism, and one carbon pool by folate were increased. Moreover, the study investigated the impact of the DMD mutation on ECs from skeletal muscles and found a significant decrease in their overall number, but no change in their proliferation. Conclusions: Overall, this study provides new insights into the gene regulatory program in ECs in DMD and highlights the importance of further research in this area.

show abstract

Section: Resultsmentioning

confidence: 99%

Uncovering the Gene Regulatory Network of Endothelial Cells in Mouse Duchenne Muscular Dystrophy: Insights from Single-Nuclei RNA Sequencing Analysis

Shen

Kim

Hamrick

et al. 2023

Biology

View full text Add to dashboard Cite

show abstract

“…We previously showed that IDH2 downregulation induced mitochondrial dysfunction by disrupting mitochondrial dynamics and increasing mitochondrial oxidative stress [ 9 ]. PINK1/Parkin-regulated mitophagy preserves mitochondrial function and concomitantly prevents endothelial senescence [ 14 , 15 ]. Therefore, we investigated the mRNA and protein levels of Sirt3, PINK1, and Parkin in IDH2-knockout HUVECs.…”

Section: Resultsmentioning

confidence: 99%

IDH2 Deficiency Promotes Endothelial Senescence by Eliciting miR-34b/c-Mediated Suppression of Mitophagy and Increased ROS Production

et al. 2023

View full text Add to dashboard Cite

Endothelial senescence impairs vascular function and thus is a primary event of age-related vasculature diseases. Isocitrate dehydrogenase 2 (IDH2) plays an important role in inducing alpha-ketoglutarate (α-KG) production and preserving mitochondrial function. However, the mechanism and regulation of IDH2 in endothelial senescence have not been elucidated. We demonstrated that downregulation of IDH2 induced accumulation of miR-34b/c, which impaired mitophagy and elevated mitochondrial reactive oxygen species (ROS) levels by inhibiting mitophagy-related markers (PTEN-induced putative kinase 1 (PINK1), Parkin, LC-II/LC3-I, and p62) and attenuating Sirtuin deacetylation 3 (Sirt3) expression. The mitochondrial dysfunction induced by IDH2 deficiency disrupted cell homeostasis and the cell cycle and led to endothelial senescence. However, miR-34b/c inhibition or α-KG supplementation restored Sirt3, PINK1, Parkin, LC-II/LC3-I, p62, and mitochondrial ROS levels, subsequently alleviating endothelial senescence. We showed that IDH2 played a crucial role in regulating endothelial senescence via induction of miR-34b/c in endothelial cells.

show abstract

“…UA inhibits mitochondrial fission, restores mitochondrial fusion and reduces the proportion of mitochondrial fragments in endothelial cells. UA enhances mitochondrial biogenesis in endothelial cells by upregulating Sirtuin 3 and peroxisome proliferator-activated receptor γ coactivator 1-α [ 81 ]. These results suggest that activation of mitochondrial autophagy may alleviate cardiac microvascular injury induced by hypoxia/reoxygenation by improving mitochondrial quality control, cell viability and proliferation.…”

Section: Reviewmentioning

confidence: 99%

Myocardial injury: where inflammation and autophagy meet

Liu

Chen

et al. 2023

Burns &Amp; Trauma

View full text Add to dashboard Cite

Autophagy is a highly conserved bulk degradation mechanism that degrades damaged organelles, aged proteins and intracellular contents to maintain the homeostasis of the intracellular microenvironment. Activation of autophagy can be observed during myocardial injury, during which inflammatory responses are strongly triggered. Autophagy can inhibit the inflammatory response and regulate the inflammatory microenvironment by removing invading pathogens and damaged mitochondria. In addition, autophagy may enhance the clearance of apoptotic and necrotic cells to promote the repair of damaged tissue. In this paper, we briefly review the role of autophagy in different cell types in the inflammatory microenvironment of myocardial injury and discuss the molecular mechanism of autophagy in regulating the inflammatory response in a series of myocardial injury conditions, including myocardial ischemia, ischemia/reperfusion injury and sepsis cardiomyopathy.

show abstract

Mitophagy alleviates ischemia/reperfusion-induced microvascular damage through improving mitochondrial quality control

Cited by 16 publications

References 60 publications

Uncovering the Gene Regulatory Network of Endothelial Cells in Mouse Duchenne Muscular Dystrophy: Insights from Single-Nuclei RNA Sequencing Analysis

Uncovering the Gene Regulatory Network of Endothelial Cells in Mouse Duchenne Muscular Dystrophy: Insights from Single-Nuclei RNA Sequencing Analysis

IDH2 Deficiency Promotes Endothelial Senescence by Eliciting miR-34b/c-Mediated Suppression of Mitophagy and Increased ROS Production

Myocardial injury: where inflammation and autophagy meet

Contact Info

Product

Resources

About