Mitochondrial GTP Metabolism Regulates Reproductive Aging

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bioRxiv. 2023 Apr 03;. doi: 10.1101/2023.04.02.535296

Lee Yi-Tang, Savini Marzia, Chen Tao, Yang Jin, Zhao Qian, Ding Lang, Gao Shihong, Senturk Mumine, Sowa Jessica, Wang Jue, Wang Meng

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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.

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bioRxiv PrePrint https://doi.org/10.1101/2023.04.02.535296

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Janelia Authors

Tao Chen

Qian Zhao

Lang Ding

Shihong Max Gao

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Mitochondrial GTP Metabolism Regulates Reproductive Aging

Abstract

Janelia Authors