A quick signal of starvation induced autophagy: Transcription versus post-translational modification of LC3

Md Razaul Karim, Hisayo Kawanago, Motoni Kadowaki

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Autophagy is the major intracellular lysosomal bulk degradation pathway induced by nutrient starvation and contributes to the elimination of damaged organelles and protein aggregates to recycle building block and is essential for cell survival. Microtubule-associated protein 1 light chain 3 (LC3) plays an indispensable role in macroautophagy formation and is a molecular marker for the process. Here, we show that autophagy increased through quick robust signaling from starvation by enhanced levels of LC3, LC3-EGFP (enhanced green fluorescent protein) punctate, and bulk proteolysis in rat hepatoma H4-II-E cells and fresh rat hepatocytes. After the addition of amino acids to the starvation condition, a similar quick signal appeared by significant reduction of the LC3 ratio and bulk proteolysis. Interestingly, we observed that post-translational modification of LC3 conversion occurred even long before the changes happened in the level of LC3-mRNA (messenger RNA) expression. A similar coordinated but diverse effect on LC3 was confirmed by using autophagy and lysosomal inhibitors. These results indicated that during starvation the initial robust signal to the cytoplasm can induce autophagy activity through modification at the protein level, whereas after depleting readily available autophagy proteins the signal goes to the DNA transcription level to maintain the autophagy capacity of cells.

Original languageEnglish (US)
Pages (from-to)28-34
Number of pages7
JournalAnalytical Biochemistry
Volume465
DOIs
StatePublished - Nov 15 2014

Bibliographical note

Funding Information:
This work was supported in part by a Grant-in-Aid for Young Scientists (B) (21780123 to M.R. Karim) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan , and a Grant-in-Aid for Scientific Research (23380074 to M. Kadowaki) from the Japan Society for the Promotion of Science . We are thankful to Noboru Mizushima (University of Tokyo) for the kind gift of LC3–EGFP plasmid.

Publisher Copyright:
© 2014 Elsevier Inc. All rights reserved.

Keywords

  • Autophagy activity
  • Autophagy capacity
  • LC3-mRNA
  • Starvation

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