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Lisak 2015 Cell Death Differ

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Publications in the MiPMap
Lisak D, Schacht T, Gawlitza A, Albrecht P, Aktas O, Koop B, Gliem M, Hofstetter HH, Zanger K, Bultynck G, Parys JB, De Smedt H, Kindler T, Adams-Quack P, Hahn M, Waisman A, Reed JC, Hövelmeyer N, Methner A (2015) BAX inhibitor-1 is a Ca2+ channel critically important for immune cell function and survival. Cell Death Differ 23:358-68.

» PMID: 26470731

Lisak D, Schacht T, Gawlitza A, Albrecht P, Aktas O, Koop B, Gliem M, Hofstetter HH, Zanger K, Bultynck G, Parys JB, De Smedt H, Kindler T, Adams-Quack P, Hahn M, Waisman A, Reed JC, Hoevelmeyer N, Methner A (2015) Cell Death Differ

Abstract: The endoplasmic reticulum (ER) serves as the major intracellular Ca2+ store and has a role in the synthesis and folding of proteins. BAX (BCL2-associated X protein) inhibitor-1 (BI-1) is a Ca2+ leak channel also implicated in the response against protein misfolding, thereby connecting the Ca2+ store and protein-folding functions of the ER. We found that BI-1-deficient mice suffer from leukopenia and erythrocytosis, have an increased number of splenic marginal zone B cells and higher abundance and nuclear translocation of NF-κB (nuclear factor-κ light-chain enhancer of activated B cells) proteins, correlating with increased cytosolic and ER Ca2+ levels. When put into culture, purified knockout T cells and even more so B cells die spontaneously. This is preceded by increased activity of the mitochondrial initiator caspase-9 and correlated with a significant surge in mitochondrial Ca2+ levels, suggesting an exhausted mitochondrial Ca2+ buffer capacity as the underlying cause for cell death in vitro. In vivo, T-cell-dependent experimental autoimmune encephalomyelitis and B-cell-dependent antibody production are attenuated, corroborating the ex vivo results. These results suggest that BI-1 has a major role in the functioning of the adaptive immune system by regulating intracellular Ca2+ homeostasis in lymphocytes.


O2k-Network Lab: DE Mainz Methner A


Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Obesity 

Organism: Mouse  Tissue;cell: Blood cells, Lymphocyte  Preparation: Intact cells 

Regulation: Calcium  Coupling state: LEAK, ROUTINE, ET  Pathway: ROX  HRR: Oxygraph-2k