@article {69613, title = {Cross-Tissue Coordination between SLC Nucleoside Transporters Regulates Reproduction in Caenorhabditis elegans}, journal = {PLoS Genet}, year = {2025}, month = {2025 May 30}, abstract = {

Metabolism is fundamental to organism physiology and pathology. From the intricate network of metabolic reactions, diverse chemical molecules, collectively termed as metabolites, are produced. In multicellular organisms, metabolite communication between different tissues is vital for maintaining homeostasis and adaptation. However, the molecular mechanisms mediating these metabolite communications remain poorly understood. Here, we focus on nucleosides and nucleotides, essential metabolites involved in multiple cellular processes, and report the pivotal role of the SLC29A family of transporters in mediating nucleoside coordination between the soma and the germline. Through genetic analysis, we discovered that two Caenorhabditis elegans homologs of SLC29A transporters, Equilibrative Nucleoside Transporter ENT-1 and ENT-2, act in the germline and the intestine, respectively, to regulate reproduction. Their knockdown synergistically results in sterility. Further single-cell transcriptomic and targeted metabolomic profiling revealed that the ENT double knockdown specifically affects genes in the purine biosynthesis pathway and reduces the ratio of guanosine to adenosine levels. Importantly, guanosine supplementation into the body cavity/pseudocoelom through microinjection rescued the sterility caused by the ENT double knockdown, whereas adenosine microinjection had no effect. Together, these studies support guanosine as a rate limiting factor in the control of reproduction, uncover the previously unknown nucleoside/nucleotide communication between the soma and the germline essential for reproductive success, and highlight the significance of SLC-mediated cell-nonautonomous metabolite coordination in regulating organism physiology.

Preprint:\ https://doi.org/10.1101/2024.09.12.612591

}, doi = {10.1371/journal.pgen.1011425}, url = {https://doi.org/10.1371/journal.pgen.1011425}, author = {Guan, Youchen and Yu, Yong and Gao, Shihong Max and Ding, Lang and Zhao, Qian and Wang, Meng} } @article {68998, title = {Mitochondrial GTP metabolism controls reproductive aging in C.~elegans.}, journal = {Developmental Cell}, year = {2023}, month = {2023 Sep 07}, 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 (mtGTP) 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 identified an age-associated increase in mitochondrial clustering surrounding oocyte nuclei, which is attenuated by 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 mtGTP levels and dynamics factors to modulate reproductive aging. These results demonstrate the significance of mtGTP metabolism in regulating oocyte mitochondrial homeostasis and reproductive longevity and identify mitochondrial fission induction as an effective strategy to improve reproductive health.

}, issn = {1878-1551}, doi = {10.1016/j.devcel.2023.08.019}, author = {Lee, Yi-Tang and Savini, Marzia and Chen, Tao and Yang, Jin and Zhao, Qian and Ding, Lang and Gao, Shihong Max and Senturk, Mumine and Sowa, Jessica N and Wang, Jue D and Wang, Meng C} } @article {69103, title = {Mitochondrial GTP metabolism controls reproductive aging in C.~elegans.}, journal = {Developmental Cell}, volume = {58}, year = {2023}, month = {2023 Dec 04}, pages = {2718-2731.e7}, 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 (mtGTP) 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 identified an age-associated increase in mitochondrial clustering surrounding oocyte nuclei, which is attenuated by 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 mtGTP levels and dynamics factors to modulate reproductive aging. These results demonstrate the significance of mtGTP metabolism in regulating oocyte mitochondrial homeostasis and reproductive longevity and identify mitochondrial fission induction as an effective strategy to improve reproductive health.

}, keywords = {Aging, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Guanosine Triphosphate, Longevity, Mitochondria, Mitochondrial Dynamics, Reproduction}, issn = {1878-1551}, doi = {10.1016/j.devcel.2023.08.019}, author = {Lee, Yi-Tang and Savini, Marzia and Chen, Tao and Yang, Jin and Zhao, Qian and Ding, Lang and Gao, Shihong Max and Senturk, Mumine and Sowa, Jessica N and Wang, Jue D and Wang, Meng C} }