Endosomal targeting and secretion of lysosomal proteins in U937 cells

The present contributions on secretion and targeting of lysosomal enzymes in U937 cells are as follows: 1. The previously described strong enhancement in the secretion of lysozyme and serglycin in the presence of PMA and a minor effect on that of procathepsin D is confirmed. 2. PMA enhances the rate of the secretion of prosaposin and this may explain the induced secretion of a portion of procathepsin D, since at least a fraction of the two precursors are engaged in mutual complexes. 3. PMA is shown to induce the secretion of a high proportion of the cellular ß-hexosaminidase indicating exocytosis of an endosomal/lysosomal compartment. 4. PMA is shown to induce secretion of a portion of partially (intermediate) and fully processed (mature) forms of cathepsin D. This and the observation referred to in preceding statement indicate an effect of PMA distally to the sorting at the TGN. 5. An induction of a fusion of a distal compartment is further supported by finding Lamp-II at the plasma membrane in PMA-treated cells. 6. Tunicamycin, which inhibits N-glycosylation and secondarily the endowment of lysosomal proteins with the M6P marker, enhances the lysosomal targeting of serglycin. This effect is strongly pronounced in the presence of PMA. It can be explained by a participation of CI-MPR in the lysosomal targeting of serglycin. The receptor may have a preference for M6P ligands, that may suppress the binding of serglycin. 7. PMA does not enhance the presence of CI-MPR at the plasma membrane. 8. The effects of PMA appear to be mediated by an activation of phospholipase D and the local generation of phosphatidic acid and diacylglycerol in the membrane. It is proposed that these lipids participate in fusion and fission phenomena of different compartments and a selective enhancement of the secretion of lysosomally targeted products. 9. PMA induces a phosphorylation of several proteins in the soluble as well as the vesicular fractions of U937 cells. One of the selectively phosphorylated proteins was identified as insulin-responsive amino peptidase (IRAP). Further experiments are indicated to explore a possible role of IRAP in the selective secretory effects of PMA

Endosomal targeting and secretion of lysosomal proteins in U937 cells

The present contributions on secretion and targeting of lysosomal enzymes in U937 cells are as follows: 1. The previously described strong enhancement in the secretion of lysozyme and serglycin in the presence of PMA and a minor effect on that of procathepsin D is confirmed. 2. PMA enhances the rate of the secretion of prosaposin and this may explain the induced secretion of a portion of procathepsin D, since at least a fraction of the two precursors are engaged in mutual complexes. 3. PMA is shown to induce the secretion of a high proportion of the cellular ß-hexosaminidase indicating exocytosis of an endosomal/lysosomal compartment. 4. PMA is shown to induce secretion of a portion of partially (intermediate) and fully processed (mature) forms of cathepsin D. This and the observation referred to in preceding statement indicate an effect of PMA distally to the sorting at the TGN. 5. An induction of a fusion of a distal compartment is further supported by finding Lamp-II at the plasma membrane in PMA-treated cells. 6. Tunicamycin, which inhibits N-glycosylation and secondarily the endowment of lysosomal proteins with the M6P marker, enhances the lysosomal targeting of serglycin. This effect is strongly pronounced in the presence of PMA. It can be explained by a participation of CI-MPR in the lysosomal targeting of serglycin. The receptor may have a preference for M6P ligands, that may suppress the binding of serglycin. 7. PMA does not enhance the presence of CI-MPR at the plasma membrane. 8. The effects of PMA appear to be mediated by an activation of phospholipase D and the local generation of phosphatidic acid and diacylglycerol in the membrane. It is proposed that these lipids participate in fusion and fission phenomena of different compartments and a selective enhancement of the secretion of lysosomally targeted products. 9. PMA induces a phosphorylation of several proteins in the soluble as well as the vesicular fractions of U937 cells. One of the selectively phosphorylated proteins was identified as insulin-responsive amino peptidase (IRAP). Further experiments are indicated to explore a possible role of IRAP in the selective secretory effects of PMA

ACT on RE+FLEX: Accelerating Coal Transition Through Repurposing Coal Plants Into Renewable and Flexibility Centers

Decarbonizing the power sector forms a critical part of the global combat against climate change. This requires inter alia retirement of the global coal power plant fleet of 2,100 GW. Although a significant part of this capacity is aging, there are complex issues that need to be addressed including the economic viability of existing coal plants in some countries relative to renewable projects and barriers to exit of coal. We have used detailed power plant level operational cost data for ten developing countries with significant share of coal and compared these with levelized cost of renewables, to demonstrate that competitiveness of coal varies significantly across different geographies. Countries like India where renewable projects have been highly competitive and there is an aging fleet of coal plants many of which are far away from mines, are already highly uncompetitive. On the other hand, countries like South Africa that have relatively inexpensive coal plants, but the average cost of renewable projects have not yet dropped sufficiently (as of 2020), will require special efforts to phase out coal completely beyond plants that have reached, or gone well past their technical life. Accelerated retirement of coal would require a new business model that allows repurposing some of these sites for alternative usage including generation from renewables, conversion of the incumbent generator into a synchronous condenser coupled with a fly wheel to provide reactive power and inertia; and installation of energy storage systems. As a repurposed coal plant for energy related activities can retain part of the workforce, it can also address some of the complex social issues. In order to develop a comprehensive repurposing program at a national level, the process needs to follow a least-cost planning methodology to identify prospective coal plant candidates for repurposing and then undertake a cost-benefit analysis of individual projects. We have demonstrated this methodology using a case study for Morocco