Deficient enzymatic activity of the mitochondrial deoxyribonucleoside kinases deoxyguanosine kinase (DGUOK) or thymidine kinase 2 (TK2) cause mitochondrial DNA (mtDNA)-depletion syndromes in humans. Here we report the generation of a Tk2-deficient mouse strain and show that the mice develop essentially normally for the first week but from then on exhibit growth retardation and die within 2-4 weeks of life. Several organs including skeletal muscle, heart, liver and spleen showed progressive loss of mtDNA without increased mtDNA mutations or structural alterations. There were no major histological changes in skeletal muscle, but heart muscle showed disorganized and damaged muscle fibers. Electron microscopy showed mitochondria with distorted cristae. The Tk2-deficient mice exhibited pronounced hypothermia and showed loss of hypodermal fat and abnormal brown adipose tissue. We conclude that Tk2 has a major role in supplying deoxyribonucleotides for mtDNA replication and that other pathways of deoxyribonucleotide synthesis cannot compensate for loss of this enzyme.

Although the mechanism of superconductivity in the cuprates remains elusive, it is generally agreed that at the heart of the problem is the physics of doped Mott insulators. A crucial step for solving the high temperature superconductivity puzzle is to elucidate the electronic structure of the parent compound and the behaviour of doped charge carriers. Here we use scanning tunnelling microscopy to investigate the atomic-scale electronic structure of the Ca 2 CuO 2 Cl 2 parent Mott insulator of the cuprates. The full electronic spectrum across the Mott-Hubbard gap is uncovered for the first time, which reveals the particle-hole symmetric and spatially uniform Hubbard bands. Defect-induced charge carriers are found to create broad in-gap electronic states that are strongly localized in space. We show that the electronic structure of pristine Mott insulator is consistent with the Zhang-Rice singlet model, but the peculiar features of the doped electronic states require further investigations.

Although the origin of high temperature superconductivity in the iron pnictides is still under debate, it is widely believed that magnetic interactions or fluctuations have a crucial role in triggering Cooper pairing. A key issue regarding the iron pnictide phase diagram is whether long-range magnetic order can coexist with superconductivity microscopically. Here we use scanning tunnelling microscopy to investigate the local electronic structure of underdoped NaFe 1 À x Co x As near the spin density wave and superconducting phase boundary. Spatially resolved spectroscopy directly reveals both the spin density wave and superconducting gaps at the same atomic location, providing compelling evidence for the microscopic coexistence of the two phases. The strengths of the two orders are shown to anti-correlate with each other, indicating the competition between them. This work implies that Cooper pairing in the iron pnictides can occur when portions of the Fermi surface are already gapped by the spin density wave order.

Dysregulation of cell metabolism is critical for the growth properties of cancer cells. The purpose of this study was to understand the role of substrate transport across the mitochondrial membrane to sustain the metabolic shift and redox defense in cancer cells. Mitochondrial carrier SLC25A10 is up-regulated in a variety of tumors and is involved in regulating intracellular levels of reactive oxygen species. We show that knockdown of SLC25A10 in A549 cells changed the growth properties to a less malignant phenotype and casued increased glutamine dependency and sensitivity to oxidative stress. The metabolic alteration was linked to an energy metabolic shift from glycolysis to mitochondrial oxidative phosphorylation illustrated by increased expression of glutamate dehydrogenase, decreased expression of lactate dehydrogenase due to down-regulation of hypoxia inducible factor 1α. We identified effects on NADPH production linked to the growth changes observed in SLC25A10 knockdown cells, demonstrated by decreased NADPH production in cells deprived of glutamine. The contribution of SLC25A10 to reprogram cell metabolism and to regulate cell growth suggests SLC25A10 as a novel target for anti-cancer strategies.

We present scanning tunneling microscopy studies of the LaOFeAs parent compound of iron pnictide superconductors. High resolution spectroscopic imaging reveals strong standing wave patterns induced by quasiparticle interference of two-dimensional surface states. Fourier analysis shows that the distribution of scattering wave vectors exhibits pronounced twofold (C(2)) symmetry, strongly reminiscent of the nematic electronic state found in CaFe(1.94)Co(0.06)As(2). The implications of these results to the electronic structure of the pnictide parent states will be discussed.