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  • Periodic Report Summary 1 - TSPO & BRAIN (Role of the mitochondrial Translocator Protein (mTSPO) in Brain Cellular Physiology: a Neglected Pathway in Signalling and Self-conservation Mechanisms)

Periodic Report Summary 1 - TSPO & BRAIN (Role of the mitochondrial Translocator Protein (mTSPO) in Brain Cellular Physiology: a Neglected Pathway in Signalling and Self-conservation Mechanisms)

In neuronalglial cells we found that TSPO acts as efficient limiting factor of the mitochondrial quality control process by inhibiting the PARK2-mediated ubiquitination of mitochondria to be disposed via targeted autophagy. We have also found that TSPO is overexpressed in stressed neuronal cells (e.g. glutamate treatment) leading to deregulation of mitochondrial Ca2+ handling and increased redox-stress. Even though this upregulation promotes an initial protective function against neuronal death it is likely –in the long term- to induce subtle, detrimental effects as indicated by the pre-clinical evidences of aged brain in which the accumulation of TSPO is evident.
The TSPO mediated generation of Reactive Oxygen Species (ROS) is the means –according to data in our hands- via which the efficiency of mitochondrial poly-ubiquitination is limited thus blocking efficient mitochondrial quality control operated by the PINK-1/PARK2 pathway.
The data, which represent the core of the results obtained so far, are summarised in the graphical abstract presented below and describe TSPO as a novel element in the regulation of mitochondrial quality control in neuronal cells and suggest this to be mediated by a selective limitation of the PARK2-mediated mitophagy.

Reported by

UNIVERSITA DEGLI STUDI DI ROMA TORVERGATA
Italy
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