Djafarzadeh 2011 Mitochondrion

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Djafarzadeh S, Vuda M, Takala J, Ochs M, Jakob SM (2011) Toll-like receptor-3-induced mitochondrial dysfunction in cultured human hepatocytes. Mitochondrion 11:83-8.

» PMID: 20691286

Djafarzadeh S, Vuda M, Takala J, Ochs M, Jakob SM (2011) Mitochondrion

Abstract: Several studies have shown the presence of liver mitochondrial dysfunction during sepsis. TLR3 recognizes viral double-stranded RNA and host endogenous cellular mRNA released from damaged cells. TLR3 ligand amplifies the systemic hyperinflammatory response observed during sepsis and in sepsis RNA escaping from damaged tissues/cells may serve as an endogenous ligand for TLR3 thereby modulating immune responses. This study addressed the hypothesis that TLR3 might regulate mitochondrial function in cultured human hepatocytes. HepG2 cells were exposed to TLR-3 ligand (dsRNA--polyinosine-polycytidylic acid; Poly I:C) and mitochondrial respiration was measured. Poly I:C induced a reduction in maximal mitochondrial respiration of human hepatocytes which was prevented partially by preincubation with cyclosporine A (a mitochondrial permeability transition pore-opening inhibitor). Poly-I:C induced activation of NF-κB, and the mitochondrial dysfunction was accompanied by caspase-8 but not caspase-3 activation and by no major alterations in cellular or mitochondrial ultrastructure.

Keywords: Toll-like receptor; Cyclosporine A; Mitochondrial permeability transition; Mitochondrial respiration; Caspase; HepG2

O2k-Network Lab: CH Bern Djafarzadeh S

Labels: MiParea: Respiration 

Organism: Human  Tissue;cell: Liver  Preparation: Permeabilized cells  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase 

Coupling state: LEAK, OXPHOS  Pathway: N, S, CIV, ROX  HRR: Oxygraph-2k 

Virus, CH