@article { , title = {A role for TSPO in mitochondrial Ca2+ homeostasis and redox stress signaling}, abstract = {The 18 kDa translocator protein TSPO localizes on the outer mitochondrial membrane (OMM). Systematically overexpressed at sites of neuroinflammation it is adopted as a biomarker of brain conditions. TSPO inhibits the autophagic removal of mitochondria by limiting PARK2-mediated mitochondrial ubiquitination via a peri-organelle accumulation of reactive oxygen species (ROS). Here we describe that TSPO deregulates mitochondrial Ca2+ signaling leading to a parallel increase in the cytosolic Ca2+ pools that activate the Ca2+-dependent NADPH oxidase (NOX) thereby increasing ROS. The inhibition of mitochondrial Ca2+ uptake by TSPO is a consequence of the phosphorylation of the voltage-dependent anion channel (VDAC1) by the protein kinase A (PKA), which is recruited to the mitochondria, in complex with the Acyl-CoA binding domain containing 3 (ACBD3). Notably, the neurotransmitter glutamate, which contributes neuronal toxicity in age-dependent conditions, triggers this TSPO-dependent mechanism of cell signaling leading to cellular demise. TSPO is therefore proposed as a novel OMM-based pathway to control intracellular Ca2+ dynamics and redox transients in neuronal cytotoxicity.}, doi = {10.1038/cddis.2017.186}, journal = {CELL DEATH \& DISEASE}, pages = {e2896}, publicationstatus = {Published}, url = {https://rvc-repository.worktribe.com/output/1391431}, volume = {8}, keyword = {ePrints migration}, year = {2017}, author = {Gatliff, J and East, D A and Singh, A and Alvarez, M S and Frison, M and Matic, I and Ferraina, C and Sampson, N and Turkheimer, F and Campanella, M} }