@article {68531,
	title = {Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity},
	journal = {eLife},
	year = {2024},
	month = {2024 Jan 19},
	abstract = {<p>Lysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins enriched at lysosomes mediate these metabolic and signaling functions. Both lysosomal metabolism and lysosomal signaling have been linked with longevity regulation; however, how lysosomes adjust their protein composition to accommodate this regulation remains unclear. Using large-scale proteomic profiling, we systemically profiled lysosome- enriched proteomes in association with different longevity mechanisms. We further discovered the lysosomal recruitment of AMPK and nucleoporin proteins and their requirements for longevity in response to increased lysosomal lipolysis. Through comparative proteomic analyses of lysosomes from different tissues and labeled with different markers, we discovered lysosomal heterogeneity across tissues as well as the specific enrichment of the Ragulator complex on Cystinosin positive lysosomes. Together, this work uncovers lysosomal proteome heterogeneity at different levels and provides resources for understanding the contribution of lysosomal proteome dynamics in modulating signal transduction, organelle crosstalk and organism longevity.</p>
},
	doi = {10.7554/eLife.85214},
	url = {https://doi.org/10.7554/eLife.85214},
	author = {Yong Yu and Shihong M. Gao and Youchen Guan and Pei-Wen Hu and Qinghao Zhang and Jiaming Liu and Bentian Jing and Qian Zhao and David M Sabatini and Monther Abu-Remaileh and Sung Yun Jung and Meng C. Wang}
}
@article {69011,
	title = {Quantitative Profiling of Lysosomal pH Heterogeneity using Fluorescence Lifetime Imaging Microscopy},
	journal = {bioRxiv},
	year = {2023},
	month = {2023 Sep 26},
	abstract = {<p>Lysosomes play crucial roles in maintaining cellular homeostasis and promoting organism fitness. The pH of lysosomes is a crucial parameter for their proper function, and it is dynamically influenced by both intracellular and environmental factors. Here, we present a method based on fluorescence lifetime imaging microscopy (FLIM) for quantitatively analyzing lysosomal pH profiles in diverse types of primary mammalian cells and in different tissues of the live organism Caenorhabditis elegans. This FLIM-based method exhibits high sensitivity in resolving subtle pH differences, thereby revealing the heterogeneity of the lysosomal population within a cell and between cell types. The method enables rapid measurement of lysosomal pH changes in response to various environmental stimuli. Furthermore, the FLIM measurement of pH-sensitive dyes circumvents the need for transgenic reporters and mitigates potential confounding factors associated with varying dye concentrations or excitation light intensity. This FLIM approach offers absolute quantification of lysosomal pH and highlights the significance of lysosomal pH heterogeneity and dynamics, providing a valuable tool for studying lysosomal functions and their regulation in various physiological and pathological contexts.</p>
},
	doi = {10.1101/2023.09.25.559395},
	url = {https://doi.org/10.1101/2023.09.25.559395},
	author = {Dinghuan Deng and Youchen Guan and Baiping Wang and Hui Zheng and Ayse Sena Mutlu and Meng Carla Wang}
}
