Alternative human eIF5A protein isoform plays a critical role in mitochondria

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Journal of Cellular Biochemistry; v. 122, n. 5 JAN 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 17/21914-1 - Caracterização funcional do aminoácido hipusina
• Beneficiário: Leticia Tamborlin
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/23620-4 - Caracterização funcional da isoforma A do fator de tradução EIF5A
• Beneficiário: Karina Danielle Pereira
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 19/06951-3 - Rastreamento das ações moleculares do aminoácido hipusina
• Beneficiário: Augusto Ducati Luchessi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/18095-0 - Estudo do fator de início de tradução de eucariotos 5A (eIF5A) em mamíferos
• Beneficiário: Augusto Ducati Luchessi
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores