@article {68531, title = {Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity}, journal = {eLife}, year = {2024}, month = {2024 Jan 19}, abstract = {

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.

}, 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 {68696, title = {Mitochondrial GTP Metabolism Regulates Reproductive Aging}, journal = {bioRxiv}, year = {2023}, month = {2023 Apr 03}, abstract = {

Healthy mitochondria are critical for reproduction. During aging, both reproductive fitness and mitochondrial homeostasis decline. Mitochondrial metabolism and dynamics are key factors in supporting mitochondrial homeostasis. However, how they are coupled to control reproductive health remains unclear. We report that mitochondrial GTP metabolism acts through mitochondrial dynamics factors to regulate reproductive aging. We discovered that germline-only inactivation of GTP- but not ATP-specific succinyl-CoA synthetase (SCS), promotes reproductive longevity in\ Caenorhabditis elegans.\ We further revealed an age-associated increase in mitochondrial clustering surrounding oocyte nuclei, which is attenuated by the GTP-specific SCS inactivation. Germline-only induction of mitochondrial fission factors sufficiently promotes mitochondrial dispersion and reproductive longevity. Moreover, we discovered that bacterial inputs affect mitochondrial GTP and dynamics factors to modulate reproductive aging. These results demonstrate the significance of mitochondrial GTP metabolism in regulating oocyte mitochondrial homeostasis and reproductive longevity and reveal mitochondrial fission induction as an effective strategy to improve reproductive health.

}, doi = {10.1101/2023.04.02.535296}, url = {https://doi.org/10.1101/2023.04.02.535296}, author = {Yi-Tang Lee and Marzia Savini and Tao Chen and Jin Yang and Qian Zhao and Lang Ding and Shihong Max Gao and Mumine Senturk and Jessica Sowa and Jue D. Wang and Meng C. Wang} }