The 18 kDa Translocator Protein (TSPO): A New Perspective in Mitochondrial Biology

Abstract

In mammals, mitochondria are central in maintaining normal cell function and dissecting the pathways that govern their physiology and pathology is therefore of utmost importance. For a long time, the science world has acknowledged the Translocator Protein (TSPO), an intriguing molecule that, through its position and association with biological processes, stands as one of the hidden regulatory pathways in mitochondrial homeostasis. Here we aim to review the literature and highlight what links TSPO to mitochondrial homeostasis in order to delineate its contribution in the functioning and malfunctioning of this critical organelle. In detail, we will discuss: 1) TSPO localization and interplay with controlling phenomena of mitochondria (e.g. mPTP); 2) TSPO interaction with the prominent mitochondrial player VDAC; consider evidence on how TSPO relates to 3) mitochondrial energy production; 4) Ca2+ signalling and 5) the generation of Reactive Oxygen Species (ROS) before finally describing 6) its part in apoptotic cell death. In essence, we hope to demonstrate the intimate involvement TSPO has in the regulation of mitochondrial homeostasis and muster attention towards this molecule, which is equally central for both cellular and mitochondrial biology.

Mitochondria and aging: A role for the mitochondrial transition pore?

“…Translocator protein is an outer mitochondrial membrane which has long been considered as a component of the mPTP and which regulates mitochondria‐mediated apoptotic cell death (Gatliff & Campanella, 2012; Morin, Musman, Pons, Berdeaux, & Ghaleh, 2016). Translocator protein expression is increased in elderly people and in patients with Alzheimer's disease (Kumar et al., 2012; Yasuno et al., 2008).…”

The impact of high and low dose ionising radiation on the central nervous system

“…Currently, TSPO deletion in mice has uncovered the role of TSPO in mitochondrial bioenergetics, as TSPO deficient mice display significant decreases in oxygen consumption [174], and produce significantly less ATP in microglial cell cultures compared to wildtype mice [151]. As the production of mitochondrial ROS is intrinsically linked to ATP production, TSPO has also been implicated in the regulation and production of ROS, and ultimately, ROS-mediated oxidative damage and apoptosis [175]. Veenman et al (2010) demonstrated that activation of TSPO facilitates ROS generation and ATP depletion, with involvement of the mitochondrial F o F 1 -ATP(synth)ase, leading to the activation of caspase-3, collapse of mitochondrial membrane potential, and the induction of apoptosis [176], [177].…”

Mechanisms Underlying Midazolam-Induced Peripheral Nerve Block and Neurotoxicity

“…[17][18][19] We suggest that midazolam is unlikely to engage TSPO-dependent apoptotic pathways in sensory neurons, given the absence of a detectable influence of PK11195 on the midazolam-induced increase in trypan blue staining. However, it is possible that binding of midazolam to TSPO leads to a reduction in mitochondrial respiration, hence reduced ATP production.…”