Maturation and Assembly Stages of IMPDH-Cytoophidia Induced by IMPDH Inhibition

نویسندگان

1 Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

2 Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

doi
10.22074/cellj.2025.2047867.1745
چکیده

Inosine-5'-monophosphate dehydrogenase (IMPDH) serves as a key regulatory enzyme, catalyzing a crucial stepin the de novo synthesis of guanine nucleotides. This enzyme plays a pivotal role in various cellular functions,including proliferation, differentiation, homeostasis, and metabolism. IMPDH has the unique ability to form proteinpolymer fibers known as IMPDH cytoophidia. These natural biological structures are integral to purine metabolismand play a significant role in regulating changes within the cellular environment. Utilizing advanced techniquessuch as immunofluorescence microscopy and Western blot analysis, we have demonstrated that ribavirin (RBV)exhibits remarkable efficacy in inducing time-dependent cytoophidia formation when compared to other IMPDHinhibitors. Our observations reveal that small filaments progressively aggregate into larger secondary structures,reaching their peak formation at 12 hours. Subsequently, the structures begin to decrease by 24 hours, and ringlikeformations dominate the cellular landscape at a remarkable 62% incidence. These findings suggest a complexand dynamic process of cytoophidia maturation in response to prolonged and time-dependent IMPDH inhibition.This process underscores the sequential emergence and development of secondary structures that surpassthe conventional ring-rod configuration. Our study provides valuable insights into the mechanisms underlyingcytoophidia formation and their potential implications for cellular regulation and metabolism.