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

King, Ben C. LU ; Renström, Erik LU and Blom, Anna M. LU (2019) In Autophagy 15(5). p.919-921
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ATG16L1, autophagy, complement C3, diabetes, intracellular complement
in
Autophagy
volume
15
issue
5
pages
3 pages
publisher
Landes Bioscience
external identifiers
  • scopus:85063935299
ISSN
1554-8627
DOI
10.1080/15548627.2019.1580515
language
English
LU publication?
yes
id
d5b5979b-49ce-4f47-b94f-e7a1b5a9724a
date added to LUP
2019-04-24 13:29:47
date last changed
2019-09-17 04:52:02
@misc{d5b5979b-49ce-4f47-b94f-e7a1b5a9724a,
  abstract     = {<p>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.</p>},
  author       = {King, Ben C. and Renström, Erik and Blom, Anna M.},
  issn         = {1554-8627},
  keyword      = {ATG16L1,autophagy,complement C3,diabetes,intracellular complement},
  language     = {eng},
  number       = {5},
  pages        = {919--921},
  publisher    = {Landes Bioscience},
  series       = {Autophagy},
  title        = {­­­Intracellular cytosolic complement component C3 regulates cytoprotective autophagy in pancreatic beta cells by interaction with ATG16L1},
  url          = {http://dx.doi.org/10.1080/15548627.2019.1580515},
  volume       = {15},
  year         = {2019},
}