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Pau B. Esparza-Moltó Cristina Nuevo-Tapioles José M. Cuezva 《Cellular and molecular life sciences : CMLS》2017,74(12):2151-2166
The mitochondrial H+-ATP synthase is a primary hub of cellular homeostasis by providing the energy required to sustain cellular activity and regulating the production of signaling molecules that reprogram nuclear activity needed for adaption to changing cues. Herein, we summarize findings regarding the regulation of the activity of the H+-ATP synthase by its physiological inhibitor, the ATPase inhibitory factor 1 (IF1) and their functional role in cellular homeostasis. First, we outline the structure and the main molecular mechanisms that regulate the activity of the enzyme. Next, we describe the molecular biology of IF1 and summarize the regulation of IF1 expression and activity as an inhibitor of the H+-ATP synthase emphasizing the role of IF1 as a main driver of energy rewiring and cellular signaling in cancer. Findings in transgenic mice in vivo indicate that the overexpression of IF1 is sufficient to reprogram energy metabolism to an enhanced glycolysis and activate reactive oxygen species (ROS)-dependent signaling pathways that promote cell survival. These findings are placed in the context of mitohormesis, a program in which a mild mitochondrial stress triggers adaptive cytoprotective mechanisms that improve lifespan. In this regard, we emphasize the role played by the H+-ATP synthase in modulating signaling pathways that activate the mitohormetic response, namely ATP, ROS and target of rapamycin (TOR). Overall, we aim to highlight the relevant role of the H+-ATP synthase and of IF1 in cellular physiology and the need of additional studies to decipher their contributions to aging and age-related diseases. 相似文献
35.
Miguel Bernabé-Rubio Miguel A. Alonso 《Cellular and molecular life sciences : CMLS》2017,74(22):4077-4095
Primary cilia are solitary, microtubule-based protrusions of the cell surface that play fundamental roles as photosensors, mechanosensors and biochemical sensors. Primary cilia dysfunction results in a long list of developmental and degenerative disorders that combine to give rise to a large spectrum of human diseases affecting almost any major body organ. Depending on the cell type, primary ciliogenesis is initiated intracellularly, as in fibroblasts, or at the cell surface, as in renal polarized epithelial cells. In this review, we have focused on the routes of primary ciliogenesis placing particular emphasis on the recently described pathway in renal polarized epithelial cells by which the midbody remnant resulting from a previous cell division event enables the centrosome for initiation of primary cilium assembly. The protein machinery implicated in primary cilium formation in epithelial cells, including the machinery best known for its involvement in establishing cell polarity and polarized membrane trafficking, is also discussed. 相似文献
36.
Liquid marbles. 总被引:5,自引:0,他引:5
The transport of a small amount of liquid on a solid is not a simple process, owing to the nature of the contact between the two phases. Setting a liquid droplet in motion requires non-negligible forces (because the contact-angle hysteresis generates a force opposing the motion), and often results in the deposition of liquid behind the drop. Different methods of levitation-electrostatic, electromagnetic, acoustic, or even simpler aerodynamic techniques-have been proposed to avoid this wetting problem, but all have proved to be rather cumbersome. Here we propose a simple alternative, which consists of encapsulating an aqueous liquid droplet with a hydrophobic powder. The resulting 'liquid marbles' are found to behave like a soft solid, and show dramatically reduced adhesion to a solid surface. As a result, motion can be generated using gravitational, electrical and magnetic fields. Moreover, because the viscous friction associated with motion is very small, we can achieve quick displacements of the droplets without any leaks. All of these features are of potential benefit in microfluidic applications, and also permit the study of a drop in a non-wetting situation-an issue of renewed interest following the recent achievement of super-hydrophobic substrates. 相似文献
37.
Olivier Darrigol 《Studies in History and Philosophy of Science Part B: Studies in History and Philosophy of Modern Physics》2009,40(2):151-166
The bewildering complexity of the history of quantum theory tends to discourage its use as a means to understand or teach the foundations of quantum mechanics. The present paper is an attempt at simplifying this history so as to make it more helpful to physicists and philosophers. In particular, Heisenberg's notoriously difficult derivation of the fundamental equations of quantum mechanics, or later derivations of its statistical interpretation are replaced with shorter and more direct arguments to the same purpose. As the implied amputations and distortions do not imply major anachronisms, they should facilitate the grasping of the main historical steps without excluding a reasonable assessment of their historical or logical necessity. 相似文献
38.
Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo 总被引:1,自引:0,他引:1
Lindholm P Voutilainen MH Laurén J Peränen J Leppänen VM Andressoo JO Lindahl M Janhunen S Kalkkinen N Timmusk T Tuominen RK Saarma M 《Nature》2007,448(7149):73-77
In Parkinson's disease, brain dopamine neurons degenerate most prominently in the substantia nigra. Neurotrophic factors promote survival, differentiation and maintenance of neurons in developing and adult vertebrate nervous system. The most potent neurotrophic factor for dopamine neurons described so far is the glial-cell-line-derived neurotrophic factor (GDNF). Here we have identified a conserved dopamine neurotrophic factor (CDNF) as a trophic factor for dopamine neurons. CDNF, together with its previously described vertebrate and invertebrate homologue the mesencephalic-astrocyte-derived neurotrophic factor, is a secreted protein with eight conserved cysteine residues, predicting a unique protein fold and defining a new, evolutionarily conserved protein family. CDNF (Armetl1) is expressed in several tissues of mouse and human, including the mouse embryonic and postnatal brain. In vivo, CDNF prevented the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons in a rat experimental model of Parkinson's disease. A single injection of CDNF before 6-OHDA delivery into the striatum significantly reduced amphetamine-induced ipsilateral turning behaviour and almost completely rescued dopaminergic tyrosine-hydroxylase-positive cells in the substantia nigra. When administered four weeks after 6-OHDA, intrastriatal injection of CDNF was able to restore the dopaminergic function and prevent the degeneration of dopaminergic neurons in substantia nigra. Thus, CDNF was at least as efficient as GDNF in both experimental settings. Our results suggest that CDNF might be beneficial for the treatment of Parkinson's disease. 相似文献
39.
Piccioni G Drossart P Sanchez-Lavega A Hueso R Taylor FW Wilson CF Grassi D Zasova L Moriconi M Adriani A Lebonnois S Coradini A Bézard B Angrilli F Arnold G Baines KH Bellucci G Benkhoff J Bibring JP Blanco A Blecka MI Carlson RW Di Lellis A Encrenaz T Erard S Fonti S Formisano V Fouchet T Garcia R Haus R Helbert J Ignatiev NI Irwin PG Langevin Y Lopez-Valverde MA Luz D Marinangeli L Orofino V Rodin AV Roos-Serote MC Saggin B Stam DM Titov D Visconti G 《Nature》2007,450(7170):637-640
Venus has no seasons, slow rotation and a very massive atmosphere, which is mainly carbon dioxide with clouds primarily of sulphuric acid droplets. Infrared observations by previous missions to Venus revealed a bright 'dipole' feature surrounded by a cold 'collar' at its north pole. The polar dipole is a 'double-eye' feature at the centre of a vast vortex that rotates around the pole, and is possibly associated with rapid downwelling. The polar cold collar is a wide, shallow river of cold air that circulates around the polar vortex. One outstanding question has been whether the global circulation was symmetric, such that a dipole feature existed at the south pole. Here we report observations of Venus' south-polar region, where we have seen clouds with morphology much like those around the north pole, but rotating somewhat faster than the northern dipole. The vortex may extend down to the lower cloud layers that lie at about 50 km height and perhaps deeper. The spectroscopic properties of the clouds around the south pole are compatible with a sulphuric acid composition. 相似文献
40.
Guerlin C Bernu J Deléglise S Sayrin C Gleyzes S Kuhr S Brune M Raimond JM Haroche S 《Nature》2007,448(7156):889-893
The irreversible evolution of a microscopic system under measurement is a central feature of quantum theory. From an initial state generally exhibiting quantum uncertainty in the measured observable, the system is projected into a state in which this observable becomes precisely known. Its value is random, with a probability determined by the initial system's state. The evolution induced by measurement (known as 'state collapse') can be progressive, accumulating the effects of elementary state changes. Here we report the observation of such a step-by-step collapse by non-destructively measuring the photon number of a field stored in a cavity. Atoms behaving as microscopic clocks cross the cavity successively. By measuring the light-induced alterations of the clock rate, information is progressively extracted, until the initially uncertain photon number converges to an integer. The suppression of the photon number spread is demonstrated by correlations between repeated measurements. The procedure illustrates all the postulates of quantum measurement (state collapse, statistical results and repeatability) and should facilitate studies of non-classical fields trapped in cavities. 相似文献