Alternative human eIF5A protein isoform plays a critical role in mitochondria

Made available in DSpace on 2021-06-25T10:20:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-05-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 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. Laboratory of Biotechnology School of Applied Sciences University of Campinas (UNICAMP) Institute of Biosciences São Paulo State University (UNESP) Department of Structural and Functional Biology Obesity and Comorbidities Research Center University of Campinas (UNICAMP) Laboratory of Cytochemistry and Immunocytochemistry Department of Biochemistry and Tissue Biology Institute of Biology University of Campinas (UNICAMP) Institute of Biosciences São Paulo State University (UNESP) FAPESP: 2010/18095-0 FAPESP: 2013/23620-4 FAPESP: 2017/21914-1 FAPESP: 2019/06951-3