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Erik Renström

Erik Renström

Vice-chancellor

Erik Renström

­­­Intracellular cytosolic complement component C3 regulates cytoprotective autophagy in pancreatic beta cells by interaction with ATG16L1

Author

  • Ben C. King
  • Erik Renström
  • Anna M. Blom

Summary, in English

Complement component C3 is central to the complement system, a humoral effector mechanism of innate immune defense. When activated, C3 covalently binds to target particles, marking them for uptake and clearance by phagocytosis. We now show that C3 also exists within the cytosol where it interacts with ATG16L1, and is therefore involved in the intracellular clearance and recycling of material by macroautophagy/autophagy in pancreatic beta cells. C3 is highly expressed in isolated human islets, and its expression is upregulated in islets isolated from diabetic patients and rodents, and correlates with patient HBA1c and body mass index (BMI). Knockout of C3 in clonal beta cells leads to dysfunctional autophagy, and increased cell death after challenge with diabetogenic stresses, which are usually alleviated by increased autophagic turnover. However, autophagic degradation of INS (insulin) granules regulates total INS content, and increased autophagy due to C3 upregulation may deplete beta cell INS stores. C3 is therefore required for efficient autophagic turnover in beta cells, and is upregulated as a cytoprotective factor during diabetes.

Department/s

  • Protein Chemistry, Malmö
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Diabetes - Islet Patophysiology

Publishing year

2019

Language

English

Pages

919-921

Publication/Series

Autophagy

Volume

15

Issue

5

Document type

Journal article (comment)

Publisher

Landes Bioscience

Topic

  • Endocrinology and Diabetes
  • Cell and Molecular Biology

Keywords

  • ATG16L1
  • autophagy
  • complement C3
  • diabetes
  • intracellular complement

Status

Published

Research group

  • Protein Chemistry, Malmö
  • Diabetes - Islet Patophysiology

ISBN/ISSN/Other

  • ISSN: 1554-8627