title: A quick signal of starvation induced autophagy: transcription versus post-translational modification of LC3.
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.
authors: Department of Applied Biological Chemistry, Faculty of Agriculture, Graduate School of Science and Technology, Niigata University, Nishi-Ku, Niigata 950-2181, Japan. Electronic address: razaulkarim_72@yahoo.com.
authors: Md Razaul
authors: MR
authors: Karim
authors: Department of Applied Biological Chemistry, Faculty of Agriculture, Graduate School of Science and Technology, Niigata University, Nishi-Ku, Niigata 950-2181, Japan.
authors: Hisayo
authors: H
authors: Kawanago
authors: Department of Applied Biological Chemistry, Faculty of Agriculture, Graduate School of Science and Technology, Niigata University, Nishi-Ku, Niigata 950-2181, Japan; Center for Transdisciplinary Research, Niigata University, Nishi-Ku, Niigata 950-2181, Japan.
authors: Motoni
authors: M
authors: Kadowaki
mesh_terms: D000818:Animals; D001343:Autophagy; D045744:Cell Line, Tumor; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013217:Starvation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; C526109:Anxa3 protein, rat
keywords: Autophagy activity; Autophagy capacity; LC3–mRNA; Starvation