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Auto-sumoylation of the yeast Ubc9 E2 SUMO-conjugating enzyme extends cellular lifespan

Author

Listed:
  • Dong-Won Jeong

    (Kyungpook National University)

  • Do Yoon Lee

    (Kyungpook National University)

  • Seung Yeon Kim

    (Kyungpook National University)

  • Seok-Won Jeoung

    (Kyungpook National University)

  • Dejian Zhao

    (Yale University)

  • James Knight

    (Yale University)

  • TuKiet T. Lam

    (Yale School of Medicine)

  • Jong Hwa Jin

    (New Drug Development Center)

  • Hyun-Shik Lee

    (Kyungpook National University)

  • Mark Hochstrasser

    (Yale University)

  • Hong-Yeoul Ryu

    (Kyungpook National University)

Abstract

Calorie restriction (CR) provides anti-aging benefits through diverse processes, such as reduced metabolism and growth and increased mitochondrial activity. Although controversy still exists regarding CR-mediated lifespan effects, many researchers are seeking interventions that mimic the effects of CR. Yeast has proven to be a useful model system for aging studies, including CR effects. We report here that yeast adapted through in vitro evolution to the severe cellular stress caused by loss of the Ulp2 SUMO-specific protease exhibit both enhanced growth rates and replicative lifespan, and they have altered gene expression profiles similar to those observed in CR. Notably, in certain evolved ulp2Δ lines, an increase in the auto-sumoylation of Ubc9 E2 SUMO-conjugating enzyme results in altered regulation of multiple targets involved in energy metabolism and translation at both transcriptional and post-translational levels. This increase is essential for the survival of aged cells and CR-mediated lifespan extension. Thus, we suggest that high Ubc9 auto-sumoylation exerts potent anti-aging effects by promoting efficient energy metabolism-driven improvements in cell replication abilities. This potential could be therapeutically explored for the development of promising CR-mimetic strategies.

Suggested Citation

  • Dong-Won Jeong & Do Yoon Lee & Seung Yeon Kim & Seok-Won Jeoung & Dejian Zhao & James Knight & TuKiet T. Lam & Jong Hwa Jin & Hyun-Shik Lee & Mark Hochstrasser & Hong-Yeoul Ryu, 2025. "Auto-sumoylation of the yeast Ubc9 E2 SUMO-conjugating enzyme extends cellular lifespan," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58925-w
    DOI: 10.1038/s41467-025-58925-w
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    References listed on IDEAS

    as
    1. Weiwei Dang & Kristan K. Steffen & Rocco Perry & Jean A. Dorsey & F. Brad Johnson & Ali Shilatifard & Matt Kaeberlein & Brian K. Kennedy & Shelley L. Berger, 2009. "Histone H4 lysine 16 acetylation regulates cellular lifespan," Nature, Nature, vol. 459(7248), pages 802-807, June.
    2. Shyr-Jiann Li & Mark Hochstrasser, 1999. "A new protease required for cell-cycle progression in yeast," Nature, Nature, vol. 398(6724), pages 246-251, March.
    3. Hong-Yeoul Ryu & Francesc López-Giráldez & James Knight & Soo Seok Hwang & Christina Renner & Stefan G. Kreft & Mark Hochstrasser, 2018. "Distinct adaptive mechanisms drive recovery from aneuploidy caused by loss of the Ulp2 SUMO protease," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
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