Search

An accurate map of intracellular organelle pH is crucial for comprehending cellular metabolism and organellar functions. However, a unified intracellular pH spectrum using a single probe is still lack. Here, we developed a novel quantum entanglement-enhanced pH-sensitive probe called SITE-pHorin, which featured a wide pH-sensitive range and ratiometric quantitative measurement capabilities. Subsequently, we measured the pH of various organelles and their sub-compartments, including mitochondrial sub-spaces, Golgi stacks, endoplasmic reticulum, lysosomes, peroxisomes, and endosomes in COS-7 cells. For the long-standing debate on mitochondrial compartments pH, we measured the pH of mitochondrial cristae as 6.60 \pm 0.40, the pH of mitochondrial intermembrane space as 6.95 \pm 0.30, and two populations of mitochondrial matrix pH at approximately 7.20 \pm 0.27 and 7.50 \pm 0.16, respectively. Notably, the lysosome pH exhibited a single, narrow Gaussian distribution centered at 4.79 \pm 0.17. Furthermore, quantum chemistry computations revealed that both the deprotonation of the residue Y182 and the discrete curvature of deformed benzene ring in chromophore are both necessary for the quantum entanglement mechanism of SITE-pHorin. Intriguingly, our findings reveal an accurate pH gradient (0.6-0.9 pH unit) between mitochondrial cristae and matrix, suggesting prior knowledge about \Delta pH (0.4-0.6) and mitochondrial proton motive force (pmf) are underestimated., Comment: 64 pages, 7 figures, the supplemental material contains 13 supplemental figures and 4 supplemental tables

Biosyntheses of proteins, nucleotides and fatty acids, are essential for the malignant proliferation and survival of cancer cells. Cumulating research findings show that amino acid restrictions are potential strategies for cancer interventions. Meanwhile, dietary strategies are popular among cancer patients. However, there is still lacking solid rationale to clarify what is the best strategy, why and how it is. Here, integrated analyses and comprehensive summaries for the abundances, signalling and functions of amino acids in proteomes, metabolism, immunity and food compositions, suggest that, intermittent fasting or intermittent dietary lysine restriction with normal maize as an intermittent staple food for days or weeks, might have the value and potential for cancer prevention or therapy. Moreover, dietary supplements were also discussed for cancer cachexia including dietary immunomodulatory., Comment: 4 figures

Mitochondria of brown adipocyte (BA) are the main intracellular sites for thermogenesis, which have been targeted for therapy to reduce obesity. However, there are long-standing critique and debates about the ability of raising cellular temperature by endogenous thermogenesis. Currently, the wrong theoretical model gave about the five orders of magnitude less than facts. Here, based on the first law of thermodynamics and thermal diffusion equation, the deduced theoretical model of mitochondrial thermogenesis satisfies Laplace equation, and is a special case for thermal diffusion equation. The model settles the long-standing questioning about the ability of raising cellular temperature by endogenous thermogenesis, and explains the thermogenic characteristics of brown adipocyte. The model and calculations also suggest that the number of free available proton is the major limiting factor for endogenous thermogenesis and its speed., Comment: 12 pages, 1 figure