Diversity of amino acid signaling pathways on autophagy regulation: A novel pathway for arginine

Aileen B. Angcajas, Norihiko Hirai, Kenji Kaneshiro, Md Razaul Karim, Yuichiro Horii, Masatoshi Kubota, Shinobu Fujimura, Motoni Kadowaki

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Autophagy is the intracellular bulk degradation process to eliminate damaged cellular machinery and to recycle building blocks, and is crucial for cell survival and cell death. Amino acids modulate autophagy in response to nutrient starvation and oxidative stress. We investigated the relevance of reactive oxygen species (ROS) production on the regulation of autophagy using amino acids, both as a mixture and individually, in rat hepatoma H4-II-E cells. Nutrient starvation elevated ROS production and stimulated autophagy. Treatment with complete (CAA), regulatory (RegAA) and non-regulatory (NonRegAA) amino acid mixtures showed significant suppression of ROS production, whereas only CAA and RegAA exhibited significant suppression of autophagy, suggesting a dissociation of the two responses. The effects of individual amino acids were examined. Leucine from RegAA decreased ROS production and suppressed autophagy. However, methionine and proline from RegAA and arginine, cystine and glutamic acid from NonRegAA suppressed autophagy with an opposite increase in ROS production. Other amino acids from the NonRegAA group showed stimulating effects on ROS production without an autophagic response. Arginine's effect on autophagy suppression was not blocked by rapamycin, indicating an mTOR-independent pathway. Inhibitor studies on arginine-regulated autophagy may indicate the involvement of NO pathway, which is independent from ROS and mTOR pathways.

Original languageEnglish (US)
Pages (from-to)8-14
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - Mar 28 2014

Bibliographical note

Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research (KAKENHI) from the Japan Society for the Promotion of Science (Grant No. 23380074 ).


  • Amino acid signaling
  • Arginine
  • Autophagy
  • NO pathway
  • ROS

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