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TSPO interacts with VDAC1 and triggers a ROS-mediated inhibition of mitochondrial quality control

Gatliff, J; East, D A; Crosby, J; Abeti, R; Harvey, R; Craigen, W; Parker, P; Campanella, M


J Gatliff

D A East

J Crosby

R Abeti

R Harvey

W Craigen

P Parker

M Campanella


The 18-kDa TSPO (translocator protein) localizes on the outer mitochondrial membrane (OMM) and participates in cholesterol transport. Here, we report that TSPO inhibits mitochondrial autophagy downstream of the PINK1-PARK2 pathway, preventing essential ubiquitination of proteins. TSPO abolishes mitochondrial relocation of SQSTM1/p62 (sequestosome 1), and consequently that of the autophagic marker LC3 (microtubule-associated protein 1 light chain 3), thus leading to an accumulation of dysfunctional mitochondria, altering the appearance of the network. Independent of cholesterol regulation, the modulation of mitophagy by TSPO is instead dependent on VDAC1 (voltage-dependent anion channel 1), to which TSPO binds, reducing mitochondrial coupling and promoting an overproduction of reactive oxygen species (ROS) that counteracts PARK2-mediated ubiquitination of proteins. These data identify TSPO as a novel element in the regulation of mitochondrial quality control by autophagy, and demonstrate the importance for cell homeostasis of its expression ratio with VDAC1.


Gatliff, J., East, D. A., Crosby, J., Abeti, R., Harvey, R., Craigen, W., …Campanella, M. (2014). TSPO interacts with VDAC1 and triggers a ROS-mediated inhibition of mitochondrial quality control. Autophagy, 10(12), 2279-96.

Journal Article Type Article
Acceptance Date Sep 22, 2014
Publication Date Dec 3, 2014
Deposit Date Feb 18, 2015
Publicly Available Date Feb 18, 2015
Journal Autophagy
Print ISSN 1554-8627
Publisher Taylor and Francis
Peer Reviewed Peer Reviewed
Volume 10
Issue 12
Pages 2279-96
Public URL


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