University of Dundee

About: University of Dundee is a education organization based out in Dundee, United Kingdom. It is known for research contribution in the topics: Population & Protein kinase A. The organization has 19258 authors who have published 39640 publications receiving 1919433 citations. The organization is also known as: Universitas Dundensis & Dundee University.

Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning.

Abstract: Loss of tuberin, the product of TSC2 gene, increases mammalian target of rapamycin (mTOR) signaling, promoting cell growth and tumor development. However, in cells expressing tuberin, it is not known how repression of mTOR signaling is relieved to activate this pathway in response to growth factors and how hamartin participates in this process. We show that hamartin colocalizes with hypophosphorylated tuberin at the membrane, where tuberin exerts its GTPase-activating protein (GAP) activity to repress Rheb signaling. In response to growth signals, tuberin is phosphorylated by AKT and translocates to the cytosol, relieving Rheb repression. Phosphorylation of tuberin at serines 939 and 981 does not alter its intrinsic GAP activity toward Rheb but partitions tuberin to the cytosol, where it is bound by 14-3-3 proteins. Thus, tuberin bound by 14-3-3 in response to AKT phosphorylation is sequestered away from its membrane-bound activation partner (hamartin) and its target GTPase (Rheb) to relieve the growth inhibitory effects of this tumor suppressor.

Nrf2 impacts cellular bioenergetics by controlling substrate availability for mitochondrial respiration

Abstract: Transcription factor Nrf2 and its repressor Keap1 regulate a network of cytoprotective genes involving more than 1% of the genome, their best known targets being drug-metabolizing and antioxidant genes. Here we demonstrate a novel role for this pathway in directly regulating mitochondrial bioenergetics in murine neurons and embryonic fibroblasts. Loss of Nrf2 leads to mitochondrial depolarisation, decreased ATP levels and impaired respiration, whereas genetic activation of Nrf2 increases the mitochondrial membrane potential and ATP levels, the rate of respiration and the efficiency of oxidative phosphorylation. We further show that Nrf2-deficient cells have increased production of ATP in glycolysis, which is then used by the F1Fo-ATPase for maintenance of the mitochondrial membrane potential. While the levels and in vitro activities of the respiratory complexes are unaffected by Nrf2 deletion, their activities in isolated mitochondria and intact live cells are substantially impaired. In addition, the rate of regeneration of NADH after inhibition of respiration is much slower in Nrf2-knockout cells than in their wild-type counterparts. Taken together, these results show that Nrf2 directly regulates cellular energy metabolism through modulating the availability of substrates for mitochondrial respiration. Our findings highlight the importance of efficient energy metabolism in Nrf2-mediated cytoprotection.

The influence of cellulose content on tensile strength in tree roots

Abstract: Root tensile strength is an important factor to consider when choosing suitable species for reinforcing soil on unstable slopes. Tensile strength has been found to increase with decreasing root diameter, however, it is not known how this phenomenon occurs. We carried out tensile tests on roots 0.2–12.0 mm in diameter of three conifer and two broadleaf species, in order to determine the relationship between tensile strength and diameter. Two species, Pinus pinaster Ait. and Castanea sativa Mill., were then chosen for a quantitative analysis of root cellulose content. Cellulose is responsible for tensile strength in wood due to its microfibrillar structure. Results showed that in all species, a significant power relationship existed between tensile strength and root diameter, with a sharp increase of tensile strength in roots with a diameter 1.0 mm, Fagus sylvatica L. was the most resistant to failure, followed by Picea abies L. and C. sativa., P. pinaster and Pinus nigra Arnold roots were the least resistant in tension for the same diameter class. Extremely high values of strength (132–201 MPa) were found in P. abies, C. sativa and P. pinaster, for the smallest roots (0.4 mm in diameter). The power relationship between tensile strength and root diameter cannot only be explained by a scaling effect typical of that found in fracture mechanics. Therefore, this relationship could be due to changes in cellulose content as the percentage of cellulose was also observed to increase with decreasing root diameter and increasing tensile strength in both P. pinaster and C. sativa.