Proteome-wide analysis of S. pombe mmd1∆ strain using reverse-protein array links eIF5A to the regulation of mitochondrial proteins

• Main Authors: Magpantay, Hilbert D., Kondo, Naoko, Matsuyama, Akihisa, Yoshida, Minoru
• Format: text
• Published: Animo Repository 2020
• Subjects: Post-translational modification; Mitochondrial membranes; Chemistry
• Online Access: https://animorepository.dlsu.edu.ph/faculty_research/11463
• Institution: De La Salle University

The eukaryotic initiation factor 5A (eIF5A) is the only known protein to undergo hypusination accomplished successively by the enzymes deoxyhypusine synthase (Dhs1) and deoxyhypusine hydroxylase (Mmd1 in S. pombe). eIF5A was initially thought to play a role in translation initiation but was later reclassified as an elongation factor due to its role in alleviating ribosomal stalling of various peptide sequences during translation elongation [1]. Here we provide evidences linking eIF5A hypusination by Mmd1 to the translation of proteins translocated to the mitochondria. Proteome-wide analysis of ~5000 S. pombe open reading frames (ORF) using the mmd1Δ S. pombe reverse-protein array identified 108 proteins whose translation is dependent on eIF5A hypusination. Functional annotation clustering analysis of these down-regulated proteins revealed enrichment of proteins translocated to the mitochondria suggesting a possible link between eIF5A hypusination and mitochondrial function. RT-PCR analysis showed that the regulation occurs at the level of translation. Our results reveal that eIF5A may be involved in translation of proteins regulating mitochondrial functions which is consistent with the fact that mitochondrial morphology and distribution is disrupted in mmd1Δ strains [2].