Crucial Roles of Ubiquitin Carboxy-Terminal Hydrolase L1 in Motor Neuronal Health by<i>Drosophila</i>Model

Truong, Huynh Kim Thoa; Thu, Trinh Thi; Anh, Huynh Man; Yoshida, Hideki; Yamaguchi, Masamitsu; Thảo, Đặng Thị Phương

doi:10.1089/ars.2021.0057

Cited by 6 publications

(3 citation statements)

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“…Previous studies show that when UCHL1 is specifically knocked out, the key proteins involved in mitochondrial oxidative phosphorylation are significantly reduced, suggesting that UCHL1 may be involved in regulation of mitochondrial content and function [ 71 ]. When dUCH (a homolog of human UCHL1) was specifically knocked down in motor neurons, the motor neuron cells exhibited aberrant morphology and function of mitochondria, such as mtDNA depletion, an increase in mitochondrial size, and overexpression of antioxidant enzymes [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

Integrative Bioinformatics Analysis Revealed Mitochondrial Dysfunction-Related Genes Underlying Intervertebral Disc Degeneration

Zhu

Tang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Objective. Mitochondrial dysfunction plays an important role in intervertebral disc degeneration (IDD). We aim to explore the pathways and key genes that cause mitochondrial dysfunction during IDD and to further reveal the pathogenesis of IDD based on bioinformatic analyses. Methods. Datasets GSE70362 and GSE124272 were downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) of mitochondrial dysfunction between IDD patients and healthy controls were screened by package limma package. Critical genes were identified by adopting gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathways, and protein-protein interaction (PPI) networks. We collected both degenerated and normal disc tissues obtained surgically, and we performed western blot and qPCR to verify the key DEGs identified in intervertebral disc tissues. Results. In total, 40 cases of IDD and 24 healthy controls were included. We identified 152 DEGs, including 67 upregulated genes and 85 downregulated genes. Four genes related to mitochondrial dysfunction (SOX9, FLVCR1, NR5A1 and UCHL1) were screened out. Of them, SOX9, FLVCR1, and UCHL1 were down-regulated in peripheral blood and intervertebral disc tissues of IDD patients, while NR5A1 was up-regulated. The analysis of immune infiltration showed the concentrations of mast cells activated were significantly the highest in IDD patients. Compared with the control group, the level of T cells CD4 memory resting was the lowest in the patients. In addition, 24 cases of IDD tissues and 12 cases of normal disc tissues were obtained to verify the results of bioinformatics analysis. Both western blot and qPCR results were consistent with the results of bioinformatics analysis. Conclusion. We identified four genes (SOX9, FLVCR1, NR5A1 and UCHL1) associated with mitochondrial dysfunction that play an important role in the progress of disc degeneration. The identification of these differential genes may provide new insights for the diagnosis and treatment of IDD.

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Section: Discussionmentioning

confidence: 99%

Integrative Bioinformatics Analysis Revealed Mitochondrial Dysfunction-Related Genes Underlying Intervertebral Disc Degeneration

Zhu

Tang

et al. 2022

Oxidative Medicine and Cellular Longevity

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show abstract

“…In skeletal muscles from mice, the loss of UCH-L1 decreases the abundance of SBHD (component of complex II) and UQCRC2 (component of complex III) proteins, whereas it increases the protein abundance of NDUFB8 (a protein of complex I) (Gao et al, 2020 ), all three proteins being components of the mitochondrial respiratory chain. Of note, deletion of the Uch-l1 gene ( dUch ) in Drosophila brain elevates the mRNA levels of the cytosolic and mitochondrial SOD (Huynh et al, 2022 ), an observation supporting a conserved functional relationship between UCH-L1 and mitochondrial proteins in fly and mammals.…”

Section: Uch-l1 and Mitochondrial Proteins And Functionsmentioning

confidence: 99%

“…In mouse muscle cells, the lack of UCH-L1 reduces the activity of the mitochondrial electron transfer chain complex II/III (Gao et al, 2020 ), which is likely to perturb the mitochondrial production of ATP. In Drosophila brains, deletion of dUch causes a severe reduction (>50%) of the ATP levels without modifying the mitochondrial membrane potential (Huynh et al, 2022 ). In contrast, the pharmacological inhibition of UCH-L1 activity with LDN-57444 has been shown to reduce the mitochondrial membrane potential of oocytes (Yuan et al, 2020 ).…”

Section: Uch-l1 and Mitochondrial Proteins And Functionsmentioning

confidence: 99%