Role of autophagy in liver regeneration

Takeo Toshima, Ken Shirabe, Yoshihiro Matsumoto, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Tomoharu Yoshizumi, Yoshihiko Maehara

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Autophagy regulates protein and organelle turnover and produces adenosine 5'-triphosphate (ATP) by using the amino acids from degraded proteins. We generated liver-specific autophagy-related gene 5 (Atg5)-knockout (KO) mice to investigate the activity of autophagy-associated pathways in liver regeneration after partial hepatectomy (PHx). The proliferation of remnant liver in Atg5 KO mice was severely impaired by 70% PHx with a reduction in postoperative mitosis, but a compensating increase in hepatocyte size. PHx injured cellular mitochondria and induced the intracellular ATP and β-oxidation reduction. Besides, hepatic accumulation of p62 and ubiquitinated proteins were enhanced. These results indicated that the reorganization of intracellular proteins and organelles during autophagy was impaired in the regenerating liver in this setting. Upregulation of p21 was associated with hepatocyte senescence and irreversible growth arrest. In the results, autophagy plays a critical role in regenerating liver and in the preservation of cellular quality by preventing hepatocytes from becoming fully senescent and hypertrophic in liver regeneration.

Original languageEnglish
Title of host publicationAutophagy
Subtitle of host publicationCancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging Volume 12
PublisherElsevier
Pages451-461
Number of pages11
ISBN (Electronic)9780128121467
ISBN (Print)9780128121474
DOIs
Publication statusPublished - Jan 1 2017

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Immunology and Microbiology(all)

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    Toshima, T., Shirabe, K., Matsumoto, Y., Itoh, S., Harimoto, N., Ikegami, T., Yoshizumi, T., & Maehara, Y. (2017). Role of autophagy in liver regeneration. In Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging Volume 12 (pp. 451-461). Elsevier. https://doi.org/10.1016/B978-0-12-812146-7.00023-8