Tetrapyrroles as Endogenous TSPO Ligands in Eukaryotes and Prokaryotes: Comparisons with Synthetic Ligands.
The 18 kDa translocator protein (TSPO) is highly 0conserved in eukaryotes and prokaryotes. Since its discovery in 1977, numerous studies established the TSPO's importance for life essential functions. For these studies, synthetic TSPO ligands typically are applied. Tetrapyrroles present endogenous ligands for the TSPO. Tetrapyrroles are also evolutionarily conserved and regulate multiple functions. TSPO and tetrapyrroles regulate each other. In animals TSPO-tetrapyrrole interactions range from effects on embryonic development to metabolism, programmed cell death, response to stress, injury and disease, and even to life span extension. In animals TSPOs are primarily located in mitochondria. In plants TSPOs are also present in plastids, the nuclear fraction, the endoplasmic reticulum, and Golgi stacks. This may contribute to translocation of tetrapyrrole intermediates across organelles' membranes. As in animals, plant TSPO binds heme and protoporphyrin IX. TSPO-tetrapyrrole interactions in plants appear to relate to development as well as stress conditions, including salt tolerance, abscisic acid-induced stress, reactive oxygen species homeostasis, and finally cell death regulation. In bacteria, TSPO is important for switching from aerobic to anaerobic metabolism, including the regulation of photosynthesis. As in mitochondria, in bacteria TSPO is located in the outer membrane. TSPO-tetrapyrrole interactions may be part of the establishment of the bacterial-eukaryote relationships, i.e., mitochondrial-eukaryote and plastid-plant endosymbiotic relationships.
Department of Neuroscience, Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Ephron Street, P.O.B. 9649, Bat-Galim, Haifa 31096, Israel. veenmanl@techunix.technion.ac.il.
Leo
L
Veenman
Department of Neuroscience, Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Ephron Street, P.O.B. 9649, Bat-Galim, Haifa 31096, Israel. alexanderv21184@gmail.com.
Alex
A
Vainshtein
Department of Neuroscience, Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Ephron Street, P.O.B. 9649, Bat-Galim, Haifa 31096, Israel. blackpearl.black2@gmail.com.
Nasra
N
Yasin
Department of Neuroscience, Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Ephron Street, P.O.B. 9649, Bat-Galim, Haifa 31096, Israel. mayabz@gmail.com.
Maya
M
Azrad
Department of Neuroscience, Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Ephron Street, P.O.B. 9649, Bat-Galim, Haifa 31096, Israel. mgavish@tx.technion.ac.il.
Moshe
M
Gavish
D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D001692:Biological Transport; D001927:Brain Diseases / Q000378:metabolism; D056890:Eukaryota / Q000378:metabolism*; D006801:Humans; D007313:Insecta / Q000378:metabolism; D008024:Ligands; D010944:Plants / Q000378:metabolism; D011387:Prokaryotic Cells / Q000378:metabolism*; D011485:Protein Binding; D011524:Protoporphyrins / Q000737:chemistry / Q000378:metabolism; D018079:Receptors, GABA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D045725:Tetrapyrroles / Q000737:chemistry / Q000378:metabolism*
D008024:Ligands; D011524:Protoporphyrins; D018079:Receptors, GABA; D045725:Tetrapyrroles; C028025:protoporphyrin IX
TSPO; TSPO binding site structures; TSPO ligand binding; cell function; eukaryotes; homeostasis; life expectancy; prokaryotes; stress; tetrapyrrole