Kopitar-Jerala 2017 Abstract MITOEAGLE Barcelona

Link: MitoEAGLE

Kopitar-Jerala N (2017)

Event: MitoEAGLE Barcelona 2017

The mitochondrion plays a critical role in cell survival, most prominently by generating the vast majority of a cell’s supply of adenosine triphosphate (ATP), but also by influencing apoptosis, cell cycle, and metabolism. Mitochondria generate ATP through aerobic respiration, whereby glucose, pyruvate, and NADH are oxidized, thus generating ROS as a byproduct. Several recent publications showed that mitochondrial ROS (mtROS) act as signaling molecules to trigger pro-inflammatory cytokine production. A recent study implicated mitochondrial complex I in LPS induction of cytokines in macrophages. It was reported that metformin, mitochondria complex I inhibitor, decreased production of the pro-form of the inflammatory cytokine IL-1β and increased the expression of the anti-inflammatory cytokine IL-10, in response to LPS in macrophages.

Stefin B (cystatin B) is an endogenous cysteine cathepsin inhibitor, and the loss-of-function mutations in the stefin B gene were reported in patients with Unverricht-Lundborg disease (EPM1). Recently, several studies implicated increased oxidative stress and inflammation in the pathology of the disease. In stefin B deficient macrophages we reported decreased IL-10 expression upon LPS stimulation and increased NLRP3 inflammasome activation Upon LPS stimulation, stefin B was targeted into the mitochondria, and the lack of stefin B resulted in the increased destabilization of mitochondrial membrane potential and mitochondrial superoxide generation. The possible role of stefin B in mitochondria will be discussed.

• Bioblast editor: Kandolf G

Labels: MiParea: Pharmacology;toxicology  Pathology: Inherited  Stress:Oxidative stress;RONS 

Regulation: Inhibitor 

Event: B2  Metformin 

Affiliations

Dept Biochem, Molecular Structural Biol, Ljubljana, Slovenia.