scholarly journals Mitochondrial Respiratory Chain Hepatopathies: Role of Liver Transplantation. A Case Series of Five Patients

2011 ◽  
pp. 5-11 ◽  
Author(s):  
Elisabeth De Greef ◽  
John Christodoulou ◽  
Ian E Alexander ◽  
Albert Shun ◽  
Edward V O’Loughlin ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Respiratory Chain ◽  
Case Series ◽  
Mitochondrial Respiratory Chain ◽  
Mitochondrial Respiratory

MITOCHONDRIAL RESPIRATORY CHAIN HEPATOPATHIES: ROLE OF LIVER TRANSPLANTATION. A CASE SERIES OF 5 PATIENTS

2008 ◽  
Vol 86 (Supplement) ◽  
pp. 617
Author(s):  
M O. Stormon ◽  
E De Greef ◽  
J Christodoulou ◽  
S Dorney ◽  
A Shun ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Respiratory Chain ◽  
Case Series ◽  
Mitochondrial Respiratory Chain ◽  
Mitochondrial Respiratory

scholarly journals Trib1 deficiency causes brown adipose respiratory chain depletion and mitochondrial disorder

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Xuelian Zhang ◽  
Bin Zhang ◽  
Chenyang Zhang ◽  
Guibo Sun ◽  
Xiaobo Sun
Keyword(s):  
Adipose Tissue ◽  
Respiratory Chain ◽  
Mitochondrial Function ◽  
Knockout Mice ◽  
Mitochondrial Respiratory Chain ◽  
Complex Iii ◽  
Adrenoceptor Agonist ◽  
Brown Adipose ◽  
Mitochondrial Respiratory

AbstractTribbles homolog 1 (TRIB1) belongs to the Tribbles family of pseudokinases, which plays a key role in tumorigenesis and inflammation. Although genome-wide analysis shows that TRIB1 expression is highly correlated with blood lipid levels, the relationship between TRIB1 and adipose tissue metabolism remains unclear. Accordingly, the aim of the present study was to explore the role of TRIB1 on mitochondrial function in the brown adipose tissue (BAT). Trib1-knockout mice were established using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology. The metabolic function of the BAT was induced by a β3-adrenoceptor agonist and the energy metabolism function of mitochondria in the BAT of mice was evaluated. Trib1-knockout mice exhibited obesity and impaired BAT thermogenesis. In particular, Trib1 knockout reduced the ability of the BAT to maintain body temperature, inhibited β3-adrenoceptor agonist-induced thermogenesis, and accelerated lipid accumulation in the liver and adipose tissues. In addition, Trib1 knockout reduced mitochondrial respiratory chain complex III activity, produced an imbalance between mitochondrial fusion and fission, caused mitochondrial structural damage and dysfunction, and affected heat production and lipid metabolism in the BAT. Conversely, overexpression of Trib1 in 3T3-L1 adipocytes increased the number of mitochondria and improved respiratory function. These findings support the role of Trib1 in regulating the mitochondrial respiratory chain and mitochondrial dynamics by affecting mitochondrial function and thermogenesis in the BAT.

ROS-Induced DNA Damage Causing Genomic Instability in CML Stem and/or Progenitor Cells and in Quiescent and/or Proliferating Cells: Role of Mitochondrial Respiratory Chain Complex III.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3268-3268
Author(s):  
Margaret Nieborowska-Skorska ◽  
Mateusz Koptyra ◽  
Elisabeth Bolton ◽  
Regina Ray ◽  
Danielle Ngaba ◽  
...  
Keyword(s):  
Dna Damage ◽  
Genomic Instability ◽  
Respiratory Chain ◽  
Chromosomal Aberrations ◽  
Oxidative Dna Damage ◽  
Mitochondrial Respiratory Chain ◽  
Complex Iii ◽  
Abl Kinase ◽  
Mitochondrial Respiratory

Abstract Abstract 3268 Poster Board III-1 BCR/ABL kinase transforms hematopoietic stem cells to induce chronic myelogenous leukemia (CML). CML in chronic phase (CML-CP) is a leukemia stem cell (LSC)-derived but leukemia progenitor cell (LPC)-driven disease, which is, in most cases, sensitive to ABL tyrosine kinase inhibitors (TKIs) monotherapy. TKIs do not eradicate the leukemia but instead usually render the disease ‘inactive', since the residual quiescent LSCs are intrinsically insensitive to BCR-ABL inhibition and, in a significant cohort of CML patients, LPCs are also refractory or acquire resistance to TKIs due to mutations in BCR/ABL kinase. In the post-imatinib era, these cells may eventually undergo transformation and initiate fatal CML blast crisis (CML-BC). The malignant progression is usually associated with enhanced expression of BCR/ABL and accumulation of additional genetic aberrations, such as TKI-resistant mutations and chromosomal aberrations. In CML-CP, LSCs and LPCs reside in the CD34+CD38- and CD34+CD38+ populations, respectively, whereas in CML-BC, LSCs are also found in the CD34+CD38+ population. In addition, LSCs and LPCs usually belong to quiescent (CFSEmax) and proliferative (CFSElow) populations, respectively. However, the origin of CML-BC clone and the role of BCR/ABL “dosage” are not known. Since genomic instability usually results from DNA damage, we investigated the mechanisms responsible for enhanced DNA damage in CML cells. Much endogenous DNA damage arises from free radicals such as reactive oxygen species (ROS). Here we show that LSCs-enriched CD34+CD38- and quiescent (CFSEmax) CML cells and LPCs-enriched CD34+CD38+ cells contain higher levels of ROS (superoxide anion, hydrogen peroxide, and hydroxyl radical) than corresponding cells from normal donors (CML-BC>CML-CP>Normal). Interestingly, CFSEmax and CFSElow CML cells displayed similar elevation of ROS indicating that the presence of BCR/ABL and not the proliferative status enhances ROS. In addition, total cellular ROS and mitochondrial ROS levels were proportional to the expression of BCR/ABL kinase implicating the role of BCR/ABL kinase “dosage”. Higher levels of ROS caused more oxidative DNA lesions, such as 8-oxoG and DNA double-strand breaks (DSBs) in CD34+ and also in CD34+CD38- CML cells than in normal counterparts (CML-BC>CML-CP>Normal). Inhibition of BCR/ABL kinase with imatinib partially reduced ROS and oxidative DNA damage in CD34+ CML-CP cells, implicating BCR/ABL-dependent and -;independent mechanisms. Our previous studies showed that elevated levels of oxidative DNA damage in BCR/ABL-transformed cells were responsible for accumulation of TKI-resistant BCR/ABL mutants and chromosomal aberrations (Blood, 2006; Leukemia, 2008), highlighting the importance of identification of the sources of ROS in CML. Mitochondrial respiratory chain (MRC) is a major site of ATP production via oxidative phosphorylation, which is associated with electron flux through MRC. Some of the electrons may escape and react with molecular oxygen to form ROS. To shut down MRC, cells were depleted of mitochondrial DNA (mtDNA) by long-term exposure to ethidium bromide in the presence of uridine and pyruvate as confirmed by RT-PCR showing the absence/reduction of mtDNA-coded Cox II gene transcript. The absence of functional MRC reduced the level of ROS by 40% and 20% in CD34+ CML-CP cells and normal counterparts, respectively, suggesting that MRC is an important source of ROS in leukemia cells. Using selective inhibitors of various MRC complexes we identified complex III as major producer of ROS in LSCs and LPCs in CML-CP. The role of complex III in CML-BC cells is somehow diminished in concordance with the observation that prolonged exposure of MRC to elevated levels of ROS results in “mitochondrial injury” and reduction of MRC activity in advanced stages of cancer. In summary, we postulate that BCR/ABL kinase generates ROS and oxidative DNA damage in a dose-dependent manner not only in LPCs-enriched CD34+CD38+ and CFSElow cells, but also in LSCs-enriched CD34+CD38- and CFSEmax cells, and that MRC complex III generates significant amount of ROS in CML-CP cells. Thus, genomic instability causing TKI resistance and progression to CML-BC may originate in LSCs as well as in LPCs. Disclosures: No relevant conflicts of interest to declare.

PS-015-Role of methylation-controlled J-protein, endogenous repressor of the mitochondrial respiratory chain, in cholestatic liver disease

2019 ◽  
Vol 70 (1) ◽  
pp. e12
Author(s):  
Paula Iruzubieta ◽  
Lucía Barbier-Torres ◽  
Naroa Goikoetxea ◽  
Teresa Cardoso Delgado ◽  
David Fernández Ramos ◽  
...  
Keyword(s):  
Liver Disease ◽  
Respiratory Chain ◽  
Mitochondrial Respiratory Chain ◽  
Cholestatic Liver Disease ◽  
J Protein ◽  
Mitochondrial Respiratory

ORTHOTOPIC LIVER TRANSPLANTATION FOR MITOCHONDRIAL RESPIRATORY CHAIN DISORDERS: A STUDY OF 5 CHILDREN1

2001 ◽  
Vol 71 (5) ◽  
pp. 633-637 ◽  
Author(s):  
Beatrice Dubern ◽  
Pierre Broue ◽  
Claire Dubuisson ◽  
Valerie Cormier-Daire ◽  
Dalila Habes ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Orthotopic Liver Transplantation ◽  
Respiratory Chain ◽  
Mitochondrial Respiratory Chain ◽  
Respiratory Chain Disorders ◽  
Mitochondrial Respiratory
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