Back

The DDIT4L-TOM40-ATP5A pathway suppresses glioblastoma oncogenesis

You, P.; Qi, Z.-X.; Luo, H.; Cai, B.; Hu, X.-Y.; Pan, J.; Gan, P.-P.; Zeng, X.-Y.; Liao, R.-J.; Tang, Q.-S.; Yu, Y.; Zhang, Z.-N.; Yang, B.-J.; Chen, L.; Zhang, X.; Li, K.-C.; Mao, Y.

2025-07-31 cancer biology
10.1101/2025.07.27.666981 bioRxiv
Show abstract

The characteristics of glioblastoma (GBM), including resistance to cell death and aberrant energy metabolism, are associated with the function of mitochondria. To date, the inherent suppressors that couple mitochondrial function with cell death remain unclear. DNA damage-inducible transcript 4-like (DDIT4L) expression in human gliomas and its association with patient survival was determined by public databases, western-blot and immunostaining. The role of DDIT4L in regulating tumor growth was analyzed using lentivirus and PDX model. The mechanism of DDIT4L on GBM mitochondrial function was determined by different assays. Here, we show that DDIT4L is an endogenous inhibitor of GBM via suppressing mitochondrial function. DDIT4L was expressed at high levels in GBM and transported into mitochondria via single import channel TOM40 other than the import receptors TOM22, TOM20 or TOM70. Then, DDIT4L interacted with the subunit of ATP synthase, inhibited mitochondrial function and induced tumor cell apoptosis. Furthermore, the synthetic peptide DDIT4LV125-P132 suppressed GBM oncogenesis. Based on these results, DDIT4L suppresses GBM oncogenesis through both TOM40- and ATP5A-dependent mechanisms to curb mitochondrial dynamics and induce cell apoptosis, and the DDIT4LV125-P132 peptide is a potential therapy for GBM.

Published in Genes & Diseases · not in our set (fewer than 10 published preprints to learn from) · training set

Matching journals

The top 12 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.