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Lysosomal amino acid efflux by proton-driven transporters is essential for lysosomal homeostasis, amino acid recycling, mTOR signaling, and maintaining lysosomal pH. To unravel the mechanisms of these transporters, we focus on cystinosin, a prototypical lysosomal amino acid transporter that exports cystine to the cytosol, where its reduction to cysteine supplies this limiting amino acid for diverse fundamental processes and controlling nutrient adaptation. Cystinosin mutations cause cystinosis, a devastating lysosomal storage disease. Here, we present structures of human cystinosin in lumen-open, cytosol-open, and cystine-bound states, which uncover the cystine recognition mechanism and capture the key conformational states of the transport cycle. Our structures, along with functional studies and double electron-electron resonance spectroscopic investigations, reveal the molecular basis for the transporters conformational transitions and protonation switch, show conformation-dependent Ragulator-Rag complex engagement, and demonstrate an unexpected activation mechanism. These findings provide molecular insights into lysosomal amino acid efflux and a potential therapeutic strategy.

Soil microbial respiration is an important source of uncertainty in projecting future climate and carbon (C) cycle feedbacks. However, its feedbacks to climate warming and underlying microbial mechanisms are still poorly understood. Here we show that the temperature sensitivity of soil microbial respiration (Q10) in a temperate grassland ecosystem persistently decreases by 12.0 ± 3.7% across 7 years of warming. Also, the shifts of microbial communities play critical roles in regulating thermal adaptation of soil respiration. Incorporating microbial functional gene abundance data into a microbially-enabled ecosystem model significantly improves the modeling performance of soil microbial respiration by 5-19%, and reduces model parametric uncertainty by 55-71%. In addition, modeling analyses show that the microbial thermal adaptation can lead to considerably less heterotrophic respiration (11.6 ± 7.5%), and hence less soil C loss. If such microbially mediated dampening effects occur generally across different spatial and temporal scales, the potential positive feedback of soil microbial respiration in response to climate warming may be less than previously predicted.

Soil microbial respiration is an important source of uncertainty in projecting future climate and carbon (C) cycle feedbacks. However, its feedbacks to climate warming and underlying microbial mechanisms are still poorly understood. Here we show that the temperature sensitivity of soil microbial respiration (Q10) in a temperate grassland ecosystem persistently decreases by 12.0 ± 3.7% across 7 years of warming. Also, the shifts of microbial communities play critical roles in regulating thermal adaptation of soil respiration. Incorporating microbial functional gene abundance data into a microbially-enabled ecosystem model significantly improves the modeling performance of soil microbial respiration by 5-19%, and reduces model parametric uncertainty by 55-71%. In addition, modeling analyses show that the microbial thermal adaptation can lead to considerably less heterotrophic respiration (11.6 ± 7.5%), and hence less soil C loss. If such microbially mediated dampening effects occur generally across different spatial and temporal scales, the potential positive feedback of soil microbial respiration in response to climate warming may be less than previously predicted.

Determining the temporal scaling of biodiversity, typically described as species-time relationships (STRs), in the face of global climate change is a central issue in ecology because it is fundamental to biodiversity preservation and ecosystem management. However, whether and how climate change affects microbial STRs remains unclear, mainly due to the scarcity of long-term experimental data. Here, we examine the STRs and phylogenetic-time relationships (PTRs) of soil bacteria and fungi in a long-term multifactorial global change experiment with warming (+3 °C), half precipitation (-50%), double precipitation (+100%) and clipping (annual plant biomass removal). Soil bacteria and fungi all exhibited strong STRs and PTRs across the 12 experimental conditions. Strikingly, warming accelerated the bacterial and fungal STR and PTR exponents (that is, the w values), yielding significantly (P < 0.001) higher temporal scaling rates. While the STRs and PTRs were significantly shifted by altered precipitation, clipping and their combinations, warming played the predominant role. In addition, comparison with the previous literature revealed that soil bacteria and fungi had considerably higher overall temporal scaling rates (w = 0.39-0.64) than those of plants and animals (w = 0.21-0.38). Our results on warming-enhanced temporal scaling of microbial biodiversity suggest that the strategies of soil biodiversity preservation and ecosystem management may need to be adjusted in a warmer world.

Determining the temporal scaling of biodiversity, typically described as species-time relationships (STRs), in the face of global climate change is a central issue in ecology because it is fundamental to biodiversity preservation and ecosystem management. However, whether and how climate change affects microbial STRs remains unclear, mainly due to the scarcity of long-term experimental data. Here, we examine the STRs and phylogenetic-time relationships (PTRs) of soil bacteria and fungi in a long-term multifactorial global change experiment with warming (+3 °C), half precipitation (-50%), double precipitation (+100%) and clipping (annual plant biomass removal). Soil bacteria and fungi all exhibited strong STRs and PTRs across the 12 experimental conditions. Strikingly, warming accelerated the bacterial and fungal STR and PTR exponents (that is, the w values), yielding significantly (P < 0.001) higher temporal scaling rates. While the STRs and PTRs were significantly shifted by altered precipitation, clipping and their combinations, warming played the predominant role. In addition, comparison with the previous literature revealed that soil bacteria and fungi had considerably higher overall temporal scaling rates (w = 0.39-0.64) than those of plants and animals (w = 0.21-0.38). Our results on warming-enhanced temporal scaling of microbial biodiversity suggest that the strategies of soil biodiversity preservation and ecosystem management may need to be adjusted in a warmer world.

Clipping, removal of aboveground plant biomass, is an important issue in grassland ecology. However, few studies have focused on the effect of clipping on belowground microbial communities. Using integrated metagenomic technologies, we examined the taxonomic and functional responses of soil microbial communities to annual clipping (2010-2014) in a grassland ecosystem of the Great Plains of North America. Our results indicated that clipping significantly (P < 0.05) increased root and microbial respiration rates. Annual temporal variation within the microbial communities was much greater than the significant changes introduced by clipping, but cumulative effects of clipping were still observed in the long-term scale. The abundances of some bacterial and fungal lineages including Actinobacteria and Bacteroidetes were significantly (P < 0.05) changed by clipping. Clipping significantly (P < 0.05) increased the abundances of labile carbon (C) degrading genes. More importantly, the abundances of recalcitrant C degrading genes were consistently and significantly (P < 0.05) increased by clipping in the last 2 years, which could accelerate recalcitrant C degradation and weaken long-term soil carbon stability. Furthermore, genes involved in nutrient-cycling processes including nitrogen cycling and phosphorus utilization were also significantly increased by clipping. The shifts of microbial communities were significantly correlated with soil respiration and plant productivity. Intriguingly, clipping effects on microbial function may be highly regulated by precipitation at the interannual scale. Altogether, our results illustrated the potential of soil microbial communities for increased soil organic matter decomposition under clipping land-use practices.

Clipping, removal of aboveground plant biomass, is an important issue in grassland ecology. However, few studies have focused on the effect of clipping on belowground microbial communities. Using integrated metagenomic technologies, we examined the taxonomic and functional responses of soil microbial communities to annual clipping (2010-2014) in a grassland ecosystem of the Great Plains of North America. Our results indicated that clipping significantly (P < 0.05) increased root and microbial respiration rates. Annual temporal variation within the microbial communities was much greater than the significant changes introduced by clipping, but cumulative effects of clipping were still observed in the long-term scale. The abundances of some bacterial and fungal lineages including Actinobacteria and Bacteroidetes were significantly (P < 0.05) changed by clipping. Clipping significantly (P < 0.05) increased the abundances of labile carbon (C) degrading genes. More importantly, the abundances of recalcitrant C degrading genes were consistently and significantly (P < 0.05) increased by clipping in the last 2 years, which could accelerate recalcitrant C degradation and weaken long-term soil carbon stability. Furthermore, genes involved in nutrient-cycling processes including nitrogen cycling and phosphorus utilization were also significantly increased by clipping. The shifts of microbial communities were significantly correlated with soil respiration and plant productivity. Intriguingly, clipping effects on microbial function may be highly regulated by precipitation at the interannual scale. Altogether, our results illustrated the potential of soil microbial communities for increased soil organic matter decomposition under clipping land-use practices.