0000000000087379
AUTHOR
Alireza Pouya
TOX3 regulates neural progenitor identity
The human genomic locus for the transcription factor TOX3 has been implicated in susceptibility to restless legs syndrome and breast cancer in genome-wide association studies, but the physiological role of TOX3 remains largely unknown. We found Tox3 to be predominantly expressed in the developing mouse brain with a peak at embryonic day E14 where it co-localizes with the neural stem and progenitor markers Nestin and Sox2 in radial glia of the ventricular zone and intermediate progenitors of the subventricular zone. Tox3 is also expressed in neural progenitor cells obtained from the ganglionic eminence of E15 mice that express Nestin, and it specifically binds the Nestin promoter in chromati…
Mitochondrial function and energy metabolism in neuronal HT22 cells resistant to oxidative stress
Background and Purpose The hippocampal cell line HT22 is an excellent model for studying the consequences of endogenous oxidative stress. Extracellular glutamate depletes cellular glutathione by blocking the glutamate/cystine antiporter system xc−. Glutathione depletion induces a well-defined programme of cell death characterized by an increase in reactive oxygen species and mitochondrial dysfunction. Experimental Approach We compared the mitochondrial shape, the abundance of mitochondrial complexes and the mitochondrial respiration of HT22 cells, selected based on their resistance to glutamate, with those of the glutamate-sensitive parental cell line. Key Results Glutamate-resistant mitoch…
The thiol switch C684 in Mitofusin-2 mediates redox-induced alterations of mitochondrial shape and respiration
Mitofusin-2 (MFN2) is a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. MFN2 also plays a role in mitochondrial fusion induced by changes in the intracellular redox state. Adding oxidized glutathione (GSSG), the core cellular stress indicator, to mitochondrial preparations stimulates mitochondrial fusion by inducing disulphide bond-mediated oligomer formation of MFN2 and its homolog MFN1 which involve cysteine 684 (C684) of MFN2. Mitochondrial hyperfusion represents an adaptive stress response that confers transient protection by increasing mitochondrial ATP production but how this depends on the thiol switch C684 in MFN2 has …