Role of eIF5A in Mitochondrial Function

Abstract

The eukaryotic translation initiation factor 5A (eIF5A) is an evolutionarily conserved protein that binds ribosomes to facilitate the translation of peptide motifs with consecutive prolines or combinations of prolines with glycine and charged amino acids. It has also been linked to other molecular functions and cellular processes, such as nuclear mRNA export and mRNA decay, proliferation, differentiation, autophagy, and apoptosis. The growing interest in eIF5A relates to its association with the pathogenesis of several diseases, including cancer, viral infection, and diabetes. It has also been proposed as an anti-aging factor: its levels decay in aged cells, whereas increasing levels of active eIF5A result in the rejuvenation of the immune and vascular systems and improved brain cognition. Recent data have linked the role of eIF5A in some pathologies with its function in maintaining healthy mitochondria. The eukaryotic translation initiation factor 5A is upregulated under respiratory metabolism and its deficiency reduces oxygen consumption, ATP production, and the levels of several mitochondrial metabolic enzymes, as well as altering mitochondria dynamics. However, although all the accumulated data strongly link eIF5A to mitochondrial function, the precise molecular role and mechanisms involved are still unknown. In this review, we discuss the findings linking eIF5A and mitochondria, speculate about its role in regulating mitochondrial homeostasis, and highlight its potential as a target in diseases related to energy metabolism.

The activator/repressor Hap1 binds to the yeast eIF5A‐encoding gene TIF51A to adapt its expression to the mitochondrial functional status

“…Eukaryotic translation initiation factor 5A (eIF5A) is a small, abundant and essential eukaryotic protein that acts as a translation elongation factor by facilitating the formation of peptide bonds between problematic amino acids, such as consecutive prolines or combinations of prolines, glycines and charged amino acids [1][2][3][4][5] (reviewed in Ref. [6]). eIF5A binds to ribosomes once activated by hypusination, a unique two-step post-translational modification carried out by the also essential enzymes deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH) (reviewed in Ref.…”

“…[7]). eIF5A assists therefore in the translation of only a part of the overall mRNA population and is essential for the synthesis of specific proteins containing eIF5A-dependent peptide motifs [6,8,9]. Additionally, eIF5A has been shown to shuttle in association with RNA and proteins from the nucleus to the cytoplasm, suggesting a role in the nuclear export of several factors [6].…”

“…eIF5A assists therefore in the translation of only a part of the overall mRNA population and is essential for the synthesis of specific proteins containing eIF5A-dependent peptide motifs [6,8,9]. Additionally, eIF5A has been shown to shuttle in association with RNA and proteins from the nucleus to the cytoplasm, suggesting a role in the nuclear export of several factors [6]. Given the role of eIF5A in the synthesis of specific proteins and its other molecular functions, this factor has been linked to a wide variety of cellular processes, including proliferation, development, cytoskeleton organization, cell migration, apoptosis and autophagy.…”

“…Given the role of eIF5A in the synthesis of specific proteins and its other molecular functions, this factor has been linked to a wide variety of cellular processes, including proliferation, development, cytoskeleton organization, cell migration, apoptosis and autophagy. Defects in eIF5A activity lead to different diseases, including cancer, viral infection, diabetes and rare neurological syndromes (reviewed in Refs [6,8,9]).…”

“…organisms and human cells have shown that depletion of active eIF5A reduces mitochondrial respiration and the expression of some mitochondrial electron transport chain (ETC) and tricarboxylic acid pathway (TCA) proteins [10,11], also yielding the overproduction of reactive oxygen species (ROS), loss of mitochondrial potential and the appearance of aberrant mitochondrial distribution. Overexpression of eIF5A also produces deleterious mitochondrial effects and induces apoptotic cell death via the intrinsic mitochondrial pathway (reviewed in Refs [6,9]). The association of eIF5A protein with mitochondria has also been reported [12][13][14][15].…”