Research Paper Volume 11, Issue 12 pp 4254—4273

Sulfate assimilation regulates hydrogen sulfide production independent of lifespan and reactive oxygen species under methionine restriction condition in yeast

Kyung-Mi Choi1, *, , Sorah Kim1, *, , Seahyun Kim1, , Hae Min Lee1, , Alaattin Kaya2, , Bok-Hwan Chun1, , Yong Kwon Lee3, , Tae-Sik Park4, , Cheol-Koo Lee1, , Seong-il Eyun5, , Byung Cheon Lee1, ,

  • 1 College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea
  • 2 Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
  • 3 Department of Culinary Art and Food Service Management, Yuhan University, Bucheon 422-749, Republic of Korea
  • 4 Department of Life Science, Gachon University, Sungnam, Republic of Korea
  • 5 Department of Life Science, Chung-Ang University, Seoul, Republic of Korea
* Equal contribution

Received: January 24, 2019       Accepted: June 18, 2019       Published: June 29, 2019
How to Cite

Copyright © 2019 Choi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Endogenously produced hydrogen sulfide was proposed to be an underlying mechanism of lifespan extension via methionine restriction. However, hydrogen sulfide regulation and its beneficial effects via methionine restriction remain elusive. Here, we identified the genes required to increase hydrogen sulfide production under methionine restriction condition using genome-wide high-throughput screening in yeast strains with single-gene deletions. Sulfate assimilation-related genes, such as MET1, MET3, MET5, and MET10, were found to be particularly crucial for hydrogen sulfide production. Interestingly, methionine restriction failed to increase hydrogen sulfide production in mutant strains; however, it successfully extended chronological lifespan and reduced reactive oxygen species levels. Altogether, our observations suggested that increased hydrogen sulfide production via methionine restriction is not the mechanism underlying extended yeast lifespan, even though increased hydrogen sulfide production occurred simultaneously with yeast lifespan extension under methionine restriction condition.


MR: methionine restriction; CR: caloric restriction; TSP: transsulfuration pathway; CBS: cystathionine β-synthase; CGL: cystathionine γ-lyase; CLS: chronological lifespan; ROS: reactive oxygen species; NaHS: sodium hydrosulfide.