Localization of nerve growth factor (NGF) receptors in the mitochondrial compartment: Characterization and putative role

BackgroundThe neurotrophin NGF receptors trkA and p75NTR are expressed in the central and peripheral nervous system as well as in non-neuronal tissues; originally described to localize to the plasma membrane, recent studies have suggested other intracellular localizations for both NGF receptors.Scope of reviewIn order to determine whether NGF receptors localize to the mitochondrial compartment mitochondria isolated from human kidney, rat tissues and a human podocyte as cell line before and after differentiation were used.Major conclusionsOur results demonstrate that NGF receptors are localized in the mitochondrial compartment of undifferentiated human podocytes and in all tissues analyzed including rat central nervous system. In mitochondria p75NTR, but not trkA, co-immunoprecipitates with the adenine nucleotide translocator (ANT) and the phosphodiesterase 4 isoform A5 (PDE4A5). Moreover, NGF, via trkA, protects isolated mitochondria of rat brain cortex from mitochondrial permeability transition induced by Ca2+.General significanceAlthough NGF receptors have been described as mainly citoplasmatic so far, we proved evidence of their expression at the mitochondrial level and their interaction with specific proteins. Our results demonstrating the expression of NGF receptors in the mitochondria provide new insights into the role of NGF at subcellular level, in different areas of the organism, including CNS.

► p75NTR and trkA are NGF cellular receptors known to localize in the plasma membrane. ► We found trkA and p75NTR in Central Nervous System and other tissues mitochondria. ► In mitochondria p75NTR interacts with ANT and PDE4A5. ► NGF protects rat brain cortex mitochondria from Ca2+induced swelling.