Role of mitochondrial translocator protein (18 kDa) on mitochondrial- related cell death processes.
The 18 kDa translocator protein (TSPO) is able to modulate several mitochondria-related cell death processes due to close association with proteins and other molecules involved to the mitochondrial permeability transition pore. In this way, herein we review cell death mechanisms targeting mitochondria, including programmed cell death type I, II and III. Several proteins involved in these cell death processes and with a possible interplay with the TSPO are also discussed including the voltage dependent anion channel, the adenine nucleotide transporter, cardiolipin, and the Bcl-2 family proteins. Noteworthy, TSPO has been also implicated in various other functions including mitochondrial respiration, immune and phagocytic host-defense response, microglial activation, inflammation, cell growth and differentiation, cancer, cell proliferation, ischemia, and mental and neuropathological disorders. We focused in recent studies of the TSPO particularly on cancer and neurodegeneration, thus presenting the TSPO as a core element in the role of mitochondria in diseases and related processes. Clinical benefit may be attainable by increasing pharmacological knowledge related to the TSPO. Recent patents typically relate to diagnosis and treatment of TSPO-related pathological conditions including cancer, and inflammatory conditions, as well as disorders associated with central nervous system, such as neurodegeneration, convulsions, anxiety, mental disorders, and dementia.
Department of Molecular Pharmacology, Technion-Israel Institute of Technology, Faculty of Medicine, Haifa, Israel.
Beatriz
B
Caballero
Leo
L
Veenman
Moshe
M
Gavish
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D016923:Cell Death; D002491:Central Nervous System Agents / Q000494:pharmacology; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010330:Patents as Topic; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction
D000970:Antineoplastic Agents; D002491:Central Nervous System Agents; D008024:Ligands; D018079:Receptors, GABA; C499229:TSPO protein, human