TSPO protein binding partners in bacteria, animals, and plants

Abstract

The ancient membrane protein TSPO is phylogenetically widespread from archaea and bacteria to insects, vertebrates, plants, and fungi. TSPO’s primary amino acid sequence is only modestly conserved between diverse species, although its five transmembrane helical structure appears mainly conserved. Its cellular location and orientation in membranes have been reported to vary between species and tissues, with implications for potential diverse binding partners and function. Most TSPO functions relate to stress-induced changes in metabolism, but in many cases it is unclear how TSPO itself functions—whether as a receptor, a sensor, a transporter, or a translocator. Much evidence suggests that TSPO acts indirectly by association with various protein binding partners or with endogenous or exogenous ligands. In this review, we focus on proteins that have most commonly been invoked as TSPO binding partners. We suggest that TSPO was originally a bacterial receptor/stress sensor associated with porphyrin binding as its most ancestral function and that it later developed additional stress-related roles in eukaryotes as its ability to bind new partners evolved.

Unde venisti PGRMC? Grand-Scale Biology from Early Eukaryotes and Eumetazoan Animal Origins

“…TSPO proteins are highly evolutionarily conserved, being found in eukaryotes, bacteria and archaea [154,155]. Like PGRMC1, mammalian TSPO's functions remain elusive.…”

Mitochondrial dynamics, Leydig cell function, and age‐related testosterone deficiency

“…TSPO is an integral protein in health whose activation can regulate cell death and promote protective and restorative responses. [31][32][33] Despite numerous studies of TSPO's role in mitochondrial function, 34 no studies have revealed why its decline in LCs leads to mitochondrial dysfunction or how this relates to reduced steroid formation. To study the potential role of TSPO in the regulation of mitochondrial function, we utilized a TSPO knockout (KO) nG1 MA-10 sub-cell line, 13 isolated LCs from rats containing a Tspo deletion, 35 and LCs isolated from aging rats with reduced TSPO levels.…”

Solid-state NMR study of structural heterogeneity of the apo WT mouse TSPO reconstituted in liposomes

“…Comparison of membrane protein reconstituted either in synthetic lipids or in bacterial cellular envelopes shows a decrease of resolution for the latter, which can be due to the presence of partners that very likely stabilizes different coexisting conformations important for the biological function [68]. TSPO functional state has been described to be linked to interaction with different partners [69]. Thus, the optimization of protein-lipids interactions and/or the presence of functional partner(s) might help in finding stabilizing conditions for mTSPO and in solving the structural heterogeneity.…”