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.

Apoptosis, ATP, Ca²+, mitochondria, ROS, TSPO

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