bims-hypusi 2026-03-01 papers

Issue of 2026–03–01
two papers selected by
Sebastian J. Hofer, Max Delbrück Center

Biol Pharm Bull. 2026 ;49(2): 355-363

Identification of Inhibitors for eIF5A2-Dependent Translation Elongation by Monitoring the Translational Efficiency of Polyproline Motif in Mitochondrial Fission Regulator 1.

Masato Suzuki, Masahiro Komeno, Ryosuke Yasumura, Ayuna Miwa, Misaki Enomoto, Hitoshi Kotani, Ken Matsumoto, Kazunori Akimoto, Chiaki Takahashi, Kazuei Igarashi, Kyohei Higashi.

We previously reported that eukaryotic translation initiation factor 5A2 (eIF5A2), rather than eIF5A1, is important for the proliferation of HeLa S3 and MDA-MB-231 cells, despite the 84% amino acid sequence identity between eIF5A1 and eIF5A2. In addition, individual upregulated genes, including mitochondrial fission regulator 1 (MTFR1), which has a proline-rich motif, by eIF5A2 were different from those in eIF5A1. Thus, eIF5A2-dependent translational elongation is a promising target for cancer treatment with minimal side effects. In this study, we constructed a high-throughput screening system to identify eIF5A2-dependent translation elongation inhibitors by monitoring the translation efficiency of the MTFR1-luciferase fusion protein in HeLa S3 cells. Orlistat and andrographolide (AGP) were suggested as inhibitors of eIF5A2-dependent translation elongation among 1744 compounds from libraries. In addition to the findings related to AGP, the present study revealed that orlistat and the silencing of eIF5A2 suppressed the invasive activity of MDA-MB-231 cells. Downregulation of heparanase 1 expression, but not of matrix metalloproteinase-2 (MMP2) and MMP9, by eIF5A2 silencing was similar to that by treatment with orlistat and AGP, suggesting that orlistat and AGP were, at least in part, capable of attenuating eIF5A2-dependent translation elongation through the repression of eIF5A2 expression. Based on these observations, monitoring the translational efficiency of MTFR1 synthesis may be useful for identifying new eIF5A2 inhibitors.

Keywords: andrographolide; eukaryotic translation initiation factor 5A2; onco-ribosome; orlistat; translation elongation

DOI: https://doi.org/10.1248/bpb.b25-00720

Mol Cell Biochem. 2026 Feb 23.

Targeting EIF5A suppresses liver fibrosis through impairment of mitochondrial function in hepatic stellate cells.

Yuzhu Di, Lubo Jin, Xiaoyu Zhang, Pengchao Deng, Feiyang Gao, Shizhu Jin.

Liver fibrosis represents a significant clinical challenge. While targeting activated hepatic stellate cells (HSCs) is a promising therapeutic strategy, the specific role of Eukaryotic Translation Initiation Factor 5 A (EIF5A) in this process remains incompletely understood. EIF5A expression was analyzed in human fibrotic liver specimens and experimental mouse models. Its therapeutic potential was evaluated through pharmacological inhibition in fibrotic mice. Direct effects and mechanisms on HSCs were further investigated in vitro, with a focus on mitochondrial function. Immunostaining revealed a marked increase of EIF5A in activated HSCs from human fibrotic livers, which was consistent with findings in mice. Inhibition of EIF5A significantly attenuated liver fibrosis in vivo. Mechanistically, EIF5A deficiency directly impaired mitochondrial function in HSCs, leading to reduced ATP production, decreased mitochondrial membrane potential, and abnormal mitochondrial morphology, thereby suppressing their activation. Our results indicate that EIF5A contributes to HSC activation during liver fibrosis, in part through modulating mitochondrial bioenergetics. The concordant observations in human and mouse systems highlight the translational relevance of EIF5A, supporting its further investigation as a potential therapeutic target for liver fibrosis.

Keywords: EIF5A; Hepatic stellate cells; Liver fibrosis; Mitochondrial

DOI: https://doi.org/10.1007/s11010-026-05504-2