IFNB/interferon-β regulates autophagy via a MIR1-TBC1D15-RAB7 pathway.

Abstract

Loss of IFNB/interferon-β in mice causes a Parkinson disease-like phenotype where many features, including SNCA/α-synuclein and MAPT/tau accumulation, can be attributed to a late-stage block in autophagic flux. Recently, we identified a mechanism that can explain this phenotype. We found that IFNB induces expression of Mir1, a microRNA that can reduce the levels of TBC1D15, a RAB GTPase-activating protein. Induction of this pathway decreases RAB7 activity and thereby stimulates macroautophagy/autophagy. The relevance of these key players is deeply conserved from humans to Caenorhabditis elegans, highlighting the importance of this ancient autophagy regulatory pathway.

• Authors: Patrick Ejlerskov, David C Rubinsztein, Roger Pocock
• Journal: Autophagy (Autophagy) Vol. 16 Issue 4 Pg. 767-769 (04 2020) ISSN: 1554-8635 [Electronic] United States
• PMID: 31958036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• GTPase-Activating Proteins
• MIRN1 microRNA, human
• MicroRNAs
• TBC1D15 protein, human
• Interferon-beta
• rab GTP-Binding Proteins

Topics

• Animals
• Autophagy (genetics, physiology)
• GTPase-Activating Proteins (metabolism)
• Humans
• Interferon-beta (metabolism)
• MicroRNAs (metabolism)
• rab GTP-Binding Proteins (metabolism)