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11.
Optic atrophy 3 as a protein of the mitochondrial outer membrane induces mitochondrial fragmentation
Seung-Wook Ryu Hyeon Joo Jeong Myunghwan Choi Mariusz Karbowski Chulhee Choi 《Cellular and molecular life sciences : CMLS》2010,67(16):2839-2850
The optic atrophy 3 (OPA3) gene, which has no known homolog or biological function, is mutated in patients with hereditary
optic neuropathies. Here, we identified OPA3 as an integral protein of the mitochondrial outer membrane (MOM), with a C-terminus
exposed to the cytosol and an N-terminal mitochondrial targeting domain. By quantitative analysis, we demonstrated that overexpression
of OPA3 significantly induced mitochondrial fragmentation, whereas OPA3 knockdown resulted in highly elongated mitochondria.
Cells with mitochondria fragmented by OPA3 did not undergo spontaneous apoptotic cell death, but were significantly sensitized
to staurosporine- and TRAIL-induced apoptosis. In contrast, overexpression of a familial OPA3 mutant (G93S) induced mitochondrial
fragmentation and spontaneous apoptosis, suggesting that OPA3 mutations may cause optic atrophy via a gain-of-function mechanism.
Together, these results indicate that OPA3, as an integral MOM protein, has a crucial role in mitochondrial fission, and provides
a direct link between mitochondrial morphology and optic atrophy. 相似文献
12.
Mirosław Zagaja Bernard Staniec Ewa Pietrykowska-Tudruj Mariusz Trytek 《Journal of Natural History》2017,51(45-46):2759-2777
Various aspects of the biology of the myrmecophilous Thiasophila angulata and T. szujeckii (Staphylinidae; Aleocharinae), mainly associated with the Formica rufa species group, are studied. The composition of defensive gland secretions from adults of T. angulata has been analysed. The complete development (egg-L1-3-pupa-adult form), including adult overwintering, of both species takes place solely in ant nests. Under laboratory conditions, this lasts for about 22 days in T. angulata, and the period elapsing between the old and new generations of insects is approximately two months. The mean fecundity of adults of this species (28 eggs) was determined, as well as the duration of its reproductive period (mean 28.5 days), and lifespan (mean 67 days). In natural conditions T. angulata, found within nests of Formica polyctena and F. rufa, produces three generations, and the sibling species T. szujeckii one generation per year. These two species differ in their phenologies and abundance dynamics of adults and larvae, which is linked to the size and temperature regime of the host nest. The results of this study uphold the recent separation of T. angulata and T. szujeckii based on morphological features of adults and selected molecular markers. Adults and larvae of T. angulata forage on both live and dead food items accumulated by the host, as well as on the host’s eggs and larvae. Both the beetle larvae and adults remain unmolested among the host workers. The adults use their defensive gland secretions, which contains substantial quantities of toxic quinones, when necessary. According to the current categories of myrmecophiles, T. angulata (and by analogy, T. szujeckii as well) should be classified as a species wholly integrated with the host. 相似文献
13.
Attwood BK Bourgognon JM Patel S Mucha M Schiavon E Skrzypiec AE Young KW Shiosaka S Korostynski M Piechota M Przewlocki R Pawlak R 《Nature》2011,473(7347):372-375
A minority of individuals experiencing traumatic events develop anxiety disorders. The reason for the lack of correspondence between the prevalence of exposure to psychological trauma and the development of anxiety is unknown. Extracellular proteolysis contributes to fear-associated responses by facilitating neuronal plasticity at the neuron-matrix interface. Here we show in mice that the serine protease neuropsin is critical for stress-related plasticity in the amygdala by regulating the dynamics of the EphB2-NMDA-receptor interaction, the expression of Fkbp5 and anxiety-like behaviour. Stress results in neuropsin-dependent cleavage of EphB2 in the amygdala causing dissociation of EphB2 from the NR1 subunit of the NMDA receptor and promoting membrane turnover of EphB2 receptors. Dynamic EphB2-NR1 interaction enhances NMDA receptor current, induces Fkbp5 gene expression and enhances behavioural signatures of anxiety. On stress, neuropsin-deficient mice do not show EphB2 cleavage and its dissociation from NR1 resulting in a static EphB2-NR1 interaction, attenuated induction of the Fkbp5 gene and low anxiety. The behavioural response to stress can be restored by intra-amygdala injection of neuropsin into neuropsin-deficient mice and disrupted by the injection of either anti-EphB2 antibodies or silencing the Fkbp5 gene in the amygdala of wild-type mice. Our findings establish a novel neuronal pathway linking stress-induced proteolysis of EphB2 in the amygdala to anxiety. 相似文献