1. Mitochondrial GTP metabolism controls reproductive aging in C. elegans.
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Lee, Yi-Tang, Savini, Marzia, Chen, Tao, Yang, Jin, Zhao, Qian, Ding, Lang, Gao, Shihong Max, Senturk, Mumine, Sowa, Jessica N., Wang, Jue D., and Wang, Meng C.
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METABOLIC regulation , *CAENORHABDITIS elegans , *HOMEOSTASIS , *MITOCHONDRIA , *BACTERIAL metabolites , *VITAMIN B12 - 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. [Display omitted] • Mitochondrial GTP-specific succinyl-CoA synthetase regulates reproductive longevity • Oocyte mitochondrial positioning influences reproductive health during aging • Mitochondrial fission in the oocyte promotes reproductive longevity • Bacterial vitamin B12 modulates reproductive aging via GTP succinyl-CoA synthetase Lee et al. identify a signaling nexus between mitochondrial GTP metabolism and mitochondrial dynamics in regulating C. elegans reproductive aging. They further demonstrate that bacterial metabolites act through this signaling mechanism to modulate the host's reproductive health during aging. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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