Decreasing Mitochondrial Fission Prevents Cholestatic Liver Injury

Yu, Tianzheng; Wang, Li; Lee, Hakjoo; O'Brien, Dawn K.; Bronk, Steven F.; Gores, Gregory J.; Yoon, Yisang

doi:10.1074/jbc.m114.588616

Cited by 34 publications

(30 citation statements)

References 66 publications

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“…Mitochondrial membrane potential was evaluated with tetramethylrhodamine ethyl ester (TMRE, Molecular Probes) and ROS levels were detected by using dihydroethidium, a fluorescent probe (DHE; Invitrogen), as described previously (Yu et al . ).…”

Section: Methodsmentioning

confidence: 97%

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Role of dynamin‐related protein 1‐mediated mitochondrial fission in resistance of mouse C2C12 myoblasts to heat injury

Deuster

Chen

2016

The Journal of Physiology

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The regulation of mitochondrial morphology is closely coupled to cell survival during stress. We examined changes in the mitochondrial morphology of mouse C2C12 skeletal muscle cells in response to heat acclimation and heat shock exposure. Acclimated cells showed a greater survival rate during heat shock exposure than non-acclimated cells, and were characterized by long interconnected mitochondria and reduced expression of dynamin-related protein 1 (Drp1) for their mitochondrial fractions. Exposure of C2C12 muscle cells to heat shock led to apoptotic death featuring activation of caspase 3/7, release of cytochrome c and loss of cell membrane integrity. Heat shock also caused excessive mitochondrial fragmentation, loss of mitochondrial membrane potential and production of reactive oxygen species in C2C12 cells. Western blot and immunofluorescence image analysis revealed translocation of Drp1 to mitochondria from the cytosol in C2C12 cells exposed to heat shock. Mitochondrial division inhibitor 1 or Drp1 gene silencer reduced mitochondrial fragmentation and increased cell viability during exposure to heat shock. These results suggest that Drp1-dependent mitochondrial fission may regulate susceptibility to heat-induced apoptosis in muscle cells and that Drp1 may serve as a target for the prevention of heat-related injury.

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Section: Methodsmentioning

confidence: 97%

“…Indirect immunofluorescence was performed as described previously (Yu et al . ). Briefly, cells cultured on coverslips were fixed in 4% paraformaldehyde and permeabilized with 0.1% Triton X‐100.…”

Section: Methodsmentioning

confidence: 97%

Role of dynamin‐related protein 1‐mediated mitochondrial fission in resistance of mouse C2C12 myoblasts to heat injury

Deuster

Chen

2016

The Journal of Physiology

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“…Mitochondria are the most important source of ROS in the liver. First, every hepatocyte contains hundreds of mitochondria, and toxic bile acids can induce mitochondrial membrane rupture to synthesize a large amount of ROS . Second, the mitochondrial electron chain can easily be disturbed, resulting in an increased electron leak to produce ROS .…”

Section: Discussionmentioning

confidence: 99%

Correlation between hepatic oxidative damage and clinical severity and mitochondrial gene sequencing results in biliary atresia

Wang

Xia

et al. 2019

Hepatology Research

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Aim To assess the level of hepatic oxidative damage and its correlation with clinical severity in biliary atresia (BA), and to understand BA mitochondrial gene sequencing. Methods Forty‐eight BA patients and 28 control subjects (20 hepatoblastoma and 8 cholestasis patients) were enrolled. Hepatic oxidative damage was assessed by the expression of oxidation and antioxidant genes, and the correlation between oxidative damage and BA incidence, liver inflammation, and fibrosis was evaluated. Moreover, 8‐hydroxyguanine (8‐OHdG), mitochondrial DNA (mtDNA) copy number, and mitochondrial gene sequences were determined to evaluate oxidative mtDNA damage in BA. Results The expression of oxidation gene cytochrome b‐245 beta chain (CYBB) in BA was significantly increased and patients with a higher CYBB expression had the higher risk of BA incidence, liver inflammation, and cirrhosis. However, the expression of antioxidant genes was significantly decreased, and glutathione S‐transferase alpha 1 (GSTA1) negatively correlated with BA incidence and cirrhosis. When GSTA1 mRNA expression was <0.5487, the sensitivity was 80.85% and the specificity was 80% for BA diagnosis. Moreover, 8‐OHdG was increased, whereas mtDNA copy number was significantly decreased in BA. Using mitochondrial gene sequencing, 10 mutation sites were identified, and one family showed a maternal inheritance in genetic loci 15 326. Conclusions In BA, oxidative damage positively correlated with BA incidence, liver inflammation, and cirrhosis. GSTA1 could be a novel diagnostic indicator. Genetic loci 15 326 could be a maternal genetic mutation site. Taken together, antioxidation therapy after Kasai surgery might have great potential in relieving liver inflammation and fibrosis in BA patients.

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“…Mitochondria also undergo significant morphological changes toward fusion upon blood meal in A. aegypti , comprising increased area, reduced density, and higher expression of the fusion mediators mitofusin and Opa1 (Gonçalves et al, ). Compelling evidence in the literature indicate that prevention of mitochondrial fission, or improvement of fusion, is beneficial in physiological and pathological states (Picard et al, ; Röth et al, ; Yu et al, ). Interestingly, maintenance of mitochondrial morphology in a fused state in mammalian models increases respiratory rates, and reduces oxidant production in distinct experimental settings (Picard et al, ).…”

Section: Does Reduced Respiratory Capacity and Mitochondrial Oxidant mentioning

confidence: 99%

Modulation of mitochondrial metabolism as a biochemical trait in blood feeding organisms: the redox vampire hypothesis redux

Ferreira

Oliveira

Paes

et al. 2018

Cell Biology International

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Hematophagous organisms undergo remarkable metabolic changes during the blood digestion process, increasing fermentative glucose metabolism, and reducing respiratory rates, both consequence of functional mitochondrial remodeling. Here, we review the pathways involved in energy metabolism and mitochondrial functionality in a comparative framework across different hematophagous species, and consider how these processes regulate redox homeostasis during blood digestion. The trend across distinct species indicate that a switch in energy metabolism might represent an important defensive mechanism to avoid the potential harmful interaction of oxidants generated from aerobic energy metabolism with products derived from blood digestion. Indeed, in insect vectors, blood feeding transiently reduces respiratory rates and oxidant production, irrespective of tissue and insect model. On the other hand, a different scenario is observed in several unrelated parasite species when exposed to blood digestion products, as respiratory rates reduce and mitochondrial oxidant production increase. The emerging picture indicates that re-wiring of energy metabolism, through reduced mitochondrial function, culminates in improved tolerance to redox insults and seems to represent a key step for hematophagous organisms to cope with the overwhelming and potentially toxic blood meal.

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Decreasing Mitochondrial Fission Prevents Cholestatic Liver Injury

Cited by 34 publications

References 66 publications

Role of dynamin‐related protein 1‐mediated mitochondrial fission in resistance of mouse C2C12 myoblasts to heat injury

Role of dynamin‐related protein 1‐mediated mitochondrial fission in resistance of mouse C2C12 myoblasts to heat injury

Correlation between hepatic oxidative damage and clinical severity and mitochondrial gene sequencing results in biliary atresia

Modulation of mitochondrial metabolism as a biochemical trait in blood feeding organisms: the redox vampire hypothesis redux

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