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Cooperative Function of Atg8- and TORC1-Mediated Activities in Yeast

Yumiko Oba1,2, Miyuki Higuchi1, Naoka Takahashi3

  • 1Department of Agriculture, Shizuoka University, Shizuoka, Japan.

Yeast (Chichester, England)
|June 26, 2025
PubMed

Insights

Autophagy-related protein 8 (Atg8) is crucial for cell survival when target of rapamycin complex 1 (TORC1) signaling is impaired. Both its lipidation-dependent and -independent functions are vital, especially under nutrient stress and metal ion exposure.

Area of Science:

  • Cellular biology
  • Molecular genetics
  • Biochemistry

Background:

  • The target of rapamycin complex 1 (TORC1) is a key regulator of cellular processes influenced by nutrient availability.
  • Autophagy-related protein 8 (Atg8) has diverse roles, including lipidation-dependent functions in autophagy and lipidation-independent functions involving Hfl1.

Purpose of the Study:

  • To investigate the role of Saccharomyces cerevisiae Atg8 in cellular responses to impaired TORC1 activity.
  • To determine the necessity of Atg8's lipidation-dependent and -independent functions for cell survival under TORC1 inhibition.

Main Methods:

  • Utilized Saccharomyces cerevisiae mutants, including atg8, atg7, hfl1, and combinations thereof.
  • Assessed cellular sensitivity to rapamycin treatment (TORC1 inhibitor) and mutated KOG1 alleles.
  • Examined responses to metal ion (Zn2+) exposure under TORC1 inhibition.

Main Results:

  • An atg8 mutant showed high sensitivity to TORC1 inhibition.
  • The atg7Δhfl1Δ double mutant exhibited defects in response to impaired TORC1 activity, indicating the importance of both Atg8 functions.
  • Both atg8Δ and atg7Δhfl1Δ mutants were sensitive to Zn2+ during low-dose rapamycin treatment.

Conclusions:

  • Both lipidation-dependent and -independent functions of Atg8 are essential for cell survival when TORC1 activity is impaired.
  • Atg8-mediated functions and TORC1 signaling are critical for cell growth, potentially through maintaining vacuole integrity.
  • These findings highlight the complex interplay between autophagy, TORC1 signaling, and cellular homeostasis.
Keywords:
Atg8Hfl1TORC1rapamycinvacuoleyeast

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