ORP4L is essential for T-cell acute lymphoblastic leukemia cell survival

Abstract

Metabolic pathways are reprogrammed in cancer to support cell survival. Here, we report that T-cell acute lymphoblastic leukemia (T-ALL) cells are characterized by increased oxidative phosphorylation and robust ATP production. We demonstrate that ORP4L is expressed in T-ALL but not normal T-cells and its abundance is proportional to cellular ATP. ORP4L acts as an adaptor/scaffold assembling CD3ɛ, Gαq/11 and PLCβ3 into a complex that activates PLCβ3. PLCβ3 catalyzes IP3 production in T-ALL as opposed to PLCγ1 in normal T-cells. Up-regulation of ORP4L thus results in a switch in the enzyme responsible for IP3-induced endoplasmic reticulum Ca2+ release and oxidative phosphorylation. ORP4L knockdown results in suboptimal bioenergetics, cell death and abrogation of T-ALL engraftment in vivo. In summary, we uncovered a signalling pathway operating specifically in T-ALL cells in which ORP4L mediates G protein-coupled ligand-induced PLCβ3 activation, resulting in an increase of mitochondrial respiration for cell survival. Targeting ORP4L might represent a promising approach for T-ALL treatment.

Analysis of ORP2‐knockout hepatocytes uncovers a novel function in actin cytoskeletal regulation

“…In the present study, we used CRISPR-Cas9-mediated gene editing to generate a complete KO of OSBPL2/ORP2 in human hepatoma cells, and performed a series of analyses to reach a comprehensive view of ORP2 function in cell physiology. The viability of the ORP2-KO cells suggested that ORP2 is not essential for cell survival, as is the case for ORP4L in specific cell types (28,29). RNA sequencing of the ORP2-KO cells revealed altered expression of .2000 mRNAs, 579 of which displayed at least 2-fold expression changes.…”

Coherent Conversion Between Microwave and Optical Photons—An Overview of Physical Implementations

“…Suitable geometries of an optical cavity include Fabry-Pérot resonator, [112] which can be readily integrated into such a scheme, and WGM resonators, as used for electro-optic approaches. [73] An alternative way to enhance the optical fields was demonstrated by Zhong et al, [127] in which a photonic crystal cavity was fabricated directly in neodymium-doped YSO without increasing the inhomogeneous linewidth of the ions in the cavity. Purcell enhancement and dipole-induced transparency were demonstrated.…”

Sustained photon pulse revivals from inhomogeneously broadened spin ensembles

“…In this work, we propose a novel approach to obtain a sustained emission of photon pulses from spin-ensembles in spite of a significant inhomogeneous broadening of the spin transition frequencies. Our concept is not restricted to a particular experimental realization of a spin ensemble, but can instead be generally applied to different physical realizations based, for instance, on negatively charged nitrogenvacancy (NV) defects in diamond [21][22][23]32], or rare-earth spin ensembles [13,33,34]. The main requirement for our theory to be applied is that the losses exhibited by each individual constituent in the ensemble, γ , are substantially smaller as compared to the bare cavity decay rate, κ.…”