Alternative human eIF5A protein isoform plays a critical role in mitochondria

Author(s)

Pereira, Karina D. ^{[1, 2]} ; Tamborlin, Leticia ^{[1, 2]} ; de Lima, I, Tanes ; Consonni, Silvio R. ^[3] ; Silveira, Leonardo R. ^[4] ; Luchessi, Augusto D. ^{[1, 2]}

Affiliation

^[1] Sao Paulo State Univ UNESP, Inst Biosci, Rio Claro, SP - Brazil

^[2] Univ Estadual Campinas, Sch Appl Sci, Lab Biotechnol, UNICAMP, Limeira, SP - Brazil

^[3] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Lab Cytochem & Immunocytochem, UNICAMP, Campinas, SP - Brazil

^[4] de Lima, Tanes, I, Univ Estadual Campinas, Obes & Comorbid Res Ctr, Dept Struct & Funct Biol, UNICAMP, Limeira, SP - Brazil

• Document type: Journal article
• Source: Journal of Cellular Biochemistry; v. 122, n. 5 JAN 2021.
• Web of Science Citations: 0

Abstract

The eukaryotic translation initiation factor 5A (eIF5A) is the only known protein containing the amino acid residue hypusine, essential for its activity. Hypusine residue is produced by a posttranslational modification involving deoxyhypusine synthetase and deoxyhypusine hydroxylase. Herein, we aimed to describe the role of the alternative human isoform A on mitochondrial processes. Isoform A depletion modulates oxidative metabolism in association with the downregulation of mitochondrial biogenesis-related genes. Through positive feedback, it increases cell respiration leading to highly reactive oxygen species production, which impacts mitochondrial bioenergetics. These metabolic changes compromise mitochondrial morphology, increasing its electron density and fission, observed by transmission electron microscopy. This set of changes leads the cells to apoptosis, evidenced by increased DNA fragmentation and proapoptotic BAK protein content increase. Thus, we show that the alternative eIF5A isoform A is crucial for energy metabolism controlled by mitochondria and cellular survival. (AU)

• FAPESP's process: 17/21914-1 - Functional characterization of the amino acid hypusine
• Grantee: Leticia Tamborlin
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/23620-4 - Functional characterization of the translation factor EIF5A isoform A
• Grantee: Karina Danielle Pereira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/06951-3 - Screening of the amino acid hypusine molecular actions
• Grantee: Augusto Ducati Luchessi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/18095-0 - Study of the eukaryotic translation initiation factor 5A (eIF5A) in mammals
• Grantee: Augusto Ducati Luchessi
• Support Opportunities: Research Grants - Young Investigators Grants