ZFIN ID: ZDB-PUB-200211-10
The AAA+ ATPase/ubiquitin ligase mysterin stabilizes cytoplasmic lipid droplets
Sugihara, M., Morito, D., Ainuki, S., Hirano, Y., Ogino, K., Kitamura, A., Hirata, H., Nagata, K.
Date: 2019
Source: The Journal of cell biology   218: 949-960 (Journal)
Registered Authors: Hirata, Hiromi
Keywords: none
MeSH Terms:
  • Adenosine Triphosphatases/genetics
  • Adenosine Triphosphatases/metabolism*
  • Animals
  • HEK293 Cells
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Lipase/genetics
  • Lipase/metabolism
  • Lipid Droplets/metabolism*
  • Lipid Metabolism*
  • Moyamoya Disease/genetics
  • Moyamoya Disease/metabolism*
  • Moyamoya Disease/pathology
  • Mutation
  • Protein Domains
  • Ubiquitin-Protein Ligases/genetics
  • Ubiquitin-Protein Ligases/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 30705059 Full text @ J. Cell Biol.
Mysterin, also known as RNF213, is an intracellular protein that forms large toroidal oligomers. Mysterin was originally identified in genetic studies of moyamoya disease (MMD), a rare cerebrovascular disorder of unknown etiology. While mysterin is known to exert ubiquitin ligase and putative mechanical ATPase activities with a RING finger domain and two adjacent AAA+ modules, its biological role is poorly understood. Here, we report that mysterin is targeted to lipid droplets (LDs), ubiquitous organelles specialized for neutral lipid storage, and markedly increases their abundance in cells. This effect was exerted primarily through specific elimination of adipose triglyceride lipase (ATGL) from LDs. The ubiquitin ligase and ATPase activities of mysterin were both important for its proper LD targeting. Notably, MMD-related mutations in the ubiquitin ligase domain of mysterin significantly impaired its fat-stabilizing activity. Our findings identify a unique new regulator of cytoplasmic LDs and suggest a potential link between the pathogenesis of MMD and fat metabolism.