Browsing by Subject "Mitophagy"

Now showing 1 - 3 of 3
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    Dynamin-related protein 1 (Drp1) mediating mitophagy contributes to the pathophysiology of nervous system diseases and brain injury
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Wu, Qiong; Luo, Cheng Liang; Tao, Lu Yang
    As the main source of energy (celluar ATP) in eukaryotic cells, mitochondria are involved in cellular physiology and pathology. The balance of mitochondrial dynamic, fission and fusion regulated by quality control mechanisms, provides a guarantee for maintaining mitochondrial function, even celluar function. Worn out mitochondria would be removed through mitophagy which is regulated by autophagy related proteins and mitochondrial membrane proteins. Drp1, dynamicrelated protein 1, is regarded as one of the most important proteins to evaluate mitochondrial fission mediating mitophagy in neurodegenerative diseases (eg. Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis) and heart failure. Recent studies have focused on the roles of Drp1 in ischemia-induced mitophagy in the hippocampal CA3 region, and traumatic brain injury (TBI)-induced cell death together with functional deficits. However, the exact mechanisms have not been well characterized. In this review, we will discuss and clarify the role of Drp1 and mitophagy in nervous system diseases and brain injury therein, with a special emphasis on their molecular mechanisms mediating mitochondrial dynamics and mitophagy
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    Ethanol-induced mitophagy in liver is associated with activation of the PINK1-Parkin pathway triggered by oxidative DNA damage
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Eid, Nabil; Ito, Yuko; Horibe, Akio; Otsuki, Yoshinori
    Mitophagy is a cytoprotective mechanism against mitochondrial damaging agents. Studies demonstrating morphological evidence for the involvement of the PINK1-Parkin pathway in the hepatocyte mitophagic response to ethanol toxicity, and potential links to apoptosis and mitochondrial alterations such as spheroid formation are still lacking. We addressed these unresolved issues using a rat model of binge alcohol exposure. Adult rats were injected with ethanol (5g/kg) and liver samples were taken at 0, 3, 6, and 24 hours after ethanol administration and processed for light and electron microscopic studies. Ethanol induced a low level of hepatocyte apoptosis, peaking at 3 h and decreasing significantly by 24 h. In contrast, there was enhanced formation of mitophagic vacuoles in the majority of normal hepatocytes of ethanol-treated rats (ETRs), which peaked at 6 h and was maintained up to 24 h based on electron microscopy and TUNEL/LC3 double labelling. Moreover, enhanced mitophagy in ETR hepatocytes was confirmed by increased LC3 puncta formation, and co-localization of Parkin and LC3 with mitochondrial and lysosomal markers. Immunoelectron microscopy demonstrated the localization of PINK1 and Parkin to damaged mitochondria of ETR hepatocytes, which was consistent with co-localization of Parkin with 8-OHdG, a marker of oxidative mitochondrial DNA damage. Furthermore, electron microscopy showed enhanced formation of mitochondrial spheroids in ETR hepatocytes. These data are the first direct morphological evidence linking PINK1-Parkin pathway activation to the enhanced mitophagic response of hepatocytes to ethanol toxicity. Ethanol-induced hepatic mitophagy may be a prosurvival mechanism, which may have therapeutic implications.
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    Open Access
    The mechanism of dexmedetomidine regulation of the HIF-1α/FUNDC1 axis in myocardial ischemia/reperfusion injury
    (2025) Yidan Huang; Zhenfei Hu; Biología Celular e Histología
    Objective. Myocardial ischemia/reperfusion injury (MIRI) is a life-threatening event that typically follows reperfusion therapy for myocardial infarction. Regarding the effects of dexmedetomidine (Dex) in MIRI, we explored its specific mechanism. Methods. The MIRI rat model was treated with Dex, Topotecan [a hypoxia-inducible factor-1α (HIF-1α) inhibitor], and lentiviral-overexpressing FUN14 domain-containing protein 1 (Lv-oe-FUNDC1), with rat heart rate analysis. The pathological damage of rat myocardial tissue was evaluated by hematoxylin-eosin (HE) and Masson staining. Positive expression levels of PTEN-induced kinase 1 (PINK1), Parkin, microtubule-associated protein 1 light chain 3 (LC3) II/I, p62 and Beclin1 proteins, HIF-1α and FUNDC1 messenger RNA (mRNA), and HIF-1α and FUNDC1 were assessed by western blot, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and immuno-histochemical staining, respectively. HIF-1α-FUNDC1 binding sites and targeted binding relationships were predicted and verified via databases and dual-luciferase assay. HIF-1α enrichment levels in the FUNDC1 promoter region were evaluated using a ChIP assay. Results. MIRI rats exhibited myocardial injury and severe myocardial dysfunction, with elevated left ventricular diastolic pressure and p62 expression, reduced left ventricular systolic pressure, and maximum rate of change in left ventricular pressure and PINK1, Parkin, LC3 II/I ratio and Beclin-1 protein levels, which were reversed by Dex treatment. MIRI rats had increased HIF-1α and FUNDC1 expression levels, which were further boosted after Dex treatment. Dex promoted mitophagy to ameliorate myocardial injury in MIRI rats via the HIF-1α/FUNDC1 axis. Conclusion. Dex promoted mitophagy by up-regulating HIF-1α to facilitate the transcriptional expression of FUNDC1, thereby ameliorating myo-cardial injury in MIRI rats.