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A role for TSPO in mitochondrial Ca2+ homeostasis and redox stress signaling

Gatliff, J; East, D A; Singh, A; Alvarez, M S; Frison, M; Matic, I; Ferraina, C; Sampson, N; Turkheimer, F; Campanella, M


J Gatliff

D A East

A Singh

M S Alvarez

M Frison

I Matic

C Ferraina

N Sampson

F Turkheimer

M Campanella


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.


Gatliff, J., East, D. A., Singh, A., Alvarez, M. S., Frison, M., Matic, I., …Campanella, M. (2017). A role for TSPO in mitochondrial Ca2+ homeostasis and redox stress signaling.

Journal Article Type Article
Acceptance Date Mar 23, 2017
Publication Date Jun 22, 2017
Deposit Date Aug 22, 2017
Publicly Available Date Aug 22, 2017
Peer Reviewed Peer Reviewed
Volume 8
Pages e2896
Public URL


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