Lisak 2015 Cell Death Differ

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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