Potential Roles of YAP/TAZ Mechanotransduction in Spaceflight-Induced Liver Dysfunction

Int J Mol Sci. 2023 Jan 22;24(3):2197. doi: 10.3390/ijms24032197.

Abstract

Microgravity exposure during spaceflight causes the disordered regulation of liver function, presenting a specialized mechano-biological coupling process. While YAP/TAZ serves as a typical mechanosensitive pathway involved in hepatocyte metabolism, it remains unclear whether and how it is correlated with microgravity-induced liver dysfunction. Here, we discussed liver function alterations induced by spaceflight or simulated effects of microgravity on Earth. The roles of YAP/TAZ serving as a potential bridge in connecting liver metabolism with microgravity were specifically summarized. Existing evidence indicated that YAP/TAZ target gene expressions were affected by mechanotransductive pathways and phase separation, reasonably speculating that microgravity might regulate YAP/TAZ activation by disrupting these pathways via cytoskeletal remodeling or nuclear deformation, or disturbing condensates formation via diffusion limit, and then breaking liver homeostasis.

Keywords: cytoskeleton; liver metabolism; mechanosensing; microgravity; nuclear deformation; phase separation.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Liver Diseases* / etiology
  • Mechanotransduction, Cellular / physiology
  • Space Flight*
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins / metabolism
  • YAP-Signaling Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • Trans-Activators
  • Transcription Factors
  • YAP-Signaling Proteins
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins