The Emerging Role of Mitochondrial Dynamics in Viral Hepatitis

2015 ◽  
pp. 354-375 ◽  
Keyword(s):  
Viral Hepatitis ◽  
Mitochondrial Dynamics

scholarly journals Role of Mitochondria in Viral Infections

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 232
Author(s):  
Srikanth Elesela ◽  
Nicholas W. Lukacs
Keyword(s):  
Viral Infections ◽  
Mitochondrial Dynamics ◽  
The Body ◽  
Viral Diseases ◽  
Multiple Organs ◽  
Innate Immune Signaling ◽  
Mitochondrial Functions ◽  
Host Virus Interactions ◽  
Virus Interactions

Viral diseases account for an increasing proportion of deaths worldwide. Viruses maneuver host cell machinery in an attempt to subvert the intracellular environment favorable for their replication. The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections. Viruses affect mitochondrial functions and impact mitochondrial metabolism, and innate immune signaling. Resurgence of host-virus interactions in recent literature emphasizes the key role of mitochondria and host metabolism on viral life processes. Mitochondrial dysfunction leads to damage of mitochondria that generate toxic compounds, importantly mitochondrial DNA, inducing systemic toxicity, leading to damage of multiple organs in the body. Mitochondrial dynamics and mitophagy are essential for the maintenance of mitochondrial quality control and homeostasis. Therefore, metabolic antagonists may be essential to gain a better understanding of viral diseases and develop effective antiviral therapeutics. This review briefly discusses how viruses exploit mitochondrial dynamics for virus proliferation and induce associated diseases.

scholarly journals Syntaxin-17-Dependent Mitochondrial Dynamics is Essential for Protection Against Oxidative-Stress-Induced Apoptosis

Antioxidants ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 522 ◽  
Author(s):  
Wang ◽  
Xiao ◽  
Huang ◽  
Liu
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Autophagic Flux ◽  
Wild Type ◽  
Dual Roles ◽  
Defective Mutant ◽  
U2os Cells ◽  
Induced Apoptosis

In this study, cell death induced by the oxidant tert-butylhydroperoxide (tBH) was observed in U2OS cells; this phenotype was rescued by Syntaxin 17 (STX17) knockout (KO) but the mechanism is unknown. STX17 plays dual roles in autophagosome–lysosome fusion and mitochondrial fission. However, the contribution of the two functions of STX17 to apoptosis has not been extensively studied. Here, we sought to dissect the dual roles of STX17 in oxidative-stress-induced apoptosis by taking advantage of STX17 knockout cells and an autophagosome–lysosome fusion defective mutant of STX17. We generated STX17 knockout U2OS cells using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and the STX17 knockout cells were reconstituted with wild-type STX17 and its autophagosome–lysosome fusion defective mutant. Autophagy was assessed by autophagic flux assay, Monomer red fluorescent protein (mRFP)–GFP–LC3 assay and protease protection assay. Golgi, endoplasmic reticulum (ER)/ER–Golgi intermediate compartment (ERGIC) and mitochondrial dynamics were examined by staining the different indicator proteins. Apoptosis was evaluated by caspase cleavage assay. The general reactive oxygen species (ROS) were detected by flow cytometry. In STX17 complete knockout cells, sealed autophagosomes were efficiently formed but their fusion with lysosomes was less defective. The fusion defect was rescued by wild-type STX17 but not the autophagosome–lysosome fusion defective mutant. No obvious defects in Golgi, ERGIC or ER dynamics were observed. Mitochondria were significantly elongated, supporting a role of STX17 in mitochondria fission and the elongation caused by STX17 KO was reversed by the autophagosome–lysosome fusion defective mutant. The clearance of protein aggregation was compromised, correlating with the autophagy defect but not with mitochondrial dynamics. This study revealed a mixed role of STX17 in autophagy, mitochondrial dynamics and oxidative stress response. STX17 knockout cells were highly resistant to oxidative stress, largely due to the function of STX17 in mitochondrial fission rather than autophagy.

scholarly journals Non-alcoholic fatty liver disease in mice with hepatocyte-specific deletion of mitochondrial fission factor

Diabetologia ◽  
2021 ◽  
Author(s):  
Yukina Takeichi ◽  
Takashi Miyazawa ◽  
Shohei Sakamoto ◽  
Yuki Hanada ◽  
Lixiang Wang ◽  
...  
Keyword(s):  
Er Stress ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Primary Hepatocytes ◽  
Alcoholic Fatty Liver ◽  
Expression Of Genes ◽  
Specific Deletion

Abstract Aims/hypothesis Mitochondria are highly dynamic organelles continuously undergoing fission and fusion, referred to as mitochondrial dynamics, to adapt to nutritional demands. Evidence suggests that impaired mitochondrial dynamics leads to metabolic abnormalities such as non-alcoholic steatohepatitis (NASH) phenotypes. However, how mitochondrial dynamics are involved in the development of NASH is poorly understood. This study aimed to elucidate the role of mitochondrial fission factor (MFF) in the development of NASH. Methods We created mice with hepatocyte-specific deletion of MFF (MffLiKO). MffLiKO mice fed normal chow diet (NCD) or high-fat diet (HFD) were evaluated for metabolic variables and their livers were examined by histological analysis. To elucidate the mechanism of development of NASH, we examined the expression of genes related to endoplasmic reticulum (ER) stress and lipid metabolism, and the secretion of triacylglycerol (TG) using the liver and primary hepatocytes isolated from MffLiKO and control mice. Results MffLiKO mice showed aberrant mitochondrial morphologies with no obvious NASH phenotypes during NCD, while they developed full-blown NASH phenotypes in response to HFD. Expression of genes related to ER stress was markedly upregulated in the liver from MffLiKO mice. In addition, expression of genes related to hepatic TG secretion was downregulated, with reduced hepatic TG secretion in MffLiKO mice in vivo and in primary cultures of MFF-deficient hepatocytes in vitro. Furthermore, thapsigargin-induced ER stress suppressed TG secretion in primary hepatocytes isolated from control mice. Conclusions/interpretation We demonstrated that ablation of MFF in liver provoked ER stress and reduced hepatic TG secretion in vivo and in vitro. Moreover, MffLiKO mice were more susceptible to HFD-induced NASH phenotype than control mice, partly because of ER stress-induced apoptosis of hepatocytes and suppression of TG secretion from hepatocytes. This study provides evidence for the role of mitochondrial fission in the development of NASH. Graphical abstract

scholarly journals The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer’s disease

2009 ◽  
Vol 109 ◽  
pp. 153-159 ◽  
Author(s):  
Xinglong Wang ◽  
Bo Su ◽  
Ling Zheng ◽  
George Perry ◽  
Mark A. Smith ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dynamics

scholarly journals Deficiency of T-Cell Intracellular Antigen 1 in Murine Embryonic Fibroblasts Is Associated with Changes in Mitochondrial Morphology and Respiration

2021 ◽  
Vol 22 (23) ◽  
pp. 12775
Author(s):  
Isabel Carrascoso ◽  
Beatriz Ramos Velasco ◽  
José M. Izquierdo
Keyword(s):  
T Cell ◽  
Rna Binding ◽  
Mitochondrial Dynamics ◽  
Rna Binding Protein ◽  
Mitochondrial Morphology ◽  
Embryonic Fibroblasts ◽  
Intracellular Antigen ◽  
Molecular Components ◽  
Shed Light

T-cell intracellular antigen 1 (TIA1) is a multifunctional RNA-binding protein involved in regulating gene expression and splicing during development and in response to environmental stress, to maintain cell homeostasis and promote survival. Herein, we used TIA1-deficient murine embryonic fibroblasts (MEFs) to study their role in mitochondria homeostasis. We found that the loss of TIA1 was associated with changes in mitochondrial morphology, promoting the appearance of elongated mitochondria with heterogeneous cristae density and size. The proteomic patterns of TIA1-deficient MEFs were consistent with expression changes in molecular components related to mitochondrial dynamics/organization and respiration. Bioenergetics analysis illustrated that TIA1 deficiency enhances mitochondrial respiration. Overall, our findings shed light on the role of TIA1 in mitochondrial dynamics and highlight a point of crosstalk between potential pro-survival and pro-senescence pathways.

scholarly journals A Scoring System For Predicting Hepatocellular Carcinoma Risk In Alcoholic Cirrhosis: A Competing Risk Analysis

2021 ◽  
Author(s):  
Kyunghan Lee ◽  
Gwang Hyeon Choi ◽  
Eun Sun Jang ◽  
Sook-Hyang Jeong ◽  
Jin–Wook Kim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Risk Analysis ◽  
Viral Hepatitis ◽  
Validation Cohort ◽  
Alcoholic Cirrhosis ◽  
Competing Risk ◽  
Competing Risk Analysis ◽  
Hazards Model ◽  
B Virus

Abstract Background & Aims: The role of hepatocellular carcinoma (HCC) surveillance is being questioned in alcoholic cirrhosis because of the relative low HCC risk. Comorbid viral hepatitis may synergistically increase the HCC risk in alcoholic cirrhosis. This study aimed to assess the risk and predictors of HCC in patients with alcoholic cirrhosis by using competing risk analysis in an area with intermediate prevalence for hepatitis B virus.Methods: A total of 965 patients with alcoholic cirrhosis were recruited at a university-affiliated hospital in Korea and randomly assigned to either the derivation (n=643) and validation (n=322) cohort. Subdistribution hazards model of Fine and Gray was used with deaths and liver transplantation treated as competing risks. Death records were confirmed from Korean government databases. A nomogram was developed to calculate the Alcohol-associated Liver Cancer Estimation (ALICE) score.Results: Markers for viral hepatitis were positive in 21.0 % and 25.8 % of patients in derivation and validation cohort, respectively. The cumulative incidence of HCC was 13.5 and 14.9 % at 10 years for derivation and validation cohort, respectively. Age, positivity for viral hepatitis markers, alpha-fetoprotein level, and platelet count were identified as independent predictors of HCC and incorporated in the ALICE score, which discriminated low, intermediate, and high risk for HCC in alcoholic cirrhosis at the cut-off of 120 and 180. Conclusions: HCC risk can be stratified by using clinical parameters including viral markers in alcoholic cirrhosis in an area where the prevalence of viral hepatitis is substantial.

scholarly journals The essential role of mitochondrial dynamics in antiviral immunity

Mitochondrion ◽  
2018 ◽  
Vol 41 ◽  
pp. 21-27 ◽  
Author(s):  
Seong-Jun Kim ◽  
Dae-Gyun Ahn ◽  
Gulam H. Syed ◽  
Aleem Siddiqui
Keyword(s):  
Essential Role ◽  
Mitochondrial Dynamics ◽  
Antiviral Immunity
Sign in / Sign up

Export Citation Format

Share Document