RESUMO
[FeFe]-hydrogenase-like genes encode [Fe4 S4]-containing proteins that are ubiquitous in eukaryotic cells. In humans, iron-only hydrogenase-like protein 1 (IOP1) represses hypoxia inducible factor-1α subunit (HIF1-α) at normal atmospheric partial O2 pressure (normoxia, 21 kPa O2). In yeasts, the nar1 mutant cannot grow at 21 kPa O2, but can develop at a lower O2 pressure (2 kPa O2). We show here that plant [FeFe]-hydrogenase-like GOLLUM genes are essential for plant development and cell cycle progression. The mutant phenotypes of these plants are seen in normoxic conditions, but not under conditions of mild hypoxia (5 kPa O2). Transcriptomic and metabolomic experiments showed that the mutation enhances the expression of some hypoxia-induced genes under normal atmospheric O2 conditions and changes the cellular content of metabolites related to energy metabolism. In conclusion, [FeFe]-hydrogenase-like proteins play a central role in eukaryotes including the adaptation of plants to the ambient O2 partial pressure.
Assuntos
Regulação Enzimológica da Expressão Gênica , Hidrogenase/genética , Proteínas Ferro-Enxofre/genética , Medicago truncatula/enzimologia , Oxigênio/metabolismo , Adaptação Fisiológica , Arabidopsis/enzimologia , Arabidopsis/genética , Arabidopsis/fisiologia , Metabolismo dos Carboidratos , Ciclo Celular , Regulação para Baixo , Metabolismo Energético , Regulação da Expressão Gênica de Plantas , Hidrogenase/metabolismo , Proteínas Ferro-Enxofre/metabolismo , Medicago truncatula/genética , Medicago truncatula/fisiologia , Metabolômica , Mutação , Fenótipo , Folhas de Planta/enzimologia , Folhas de Planta/genética , Folhas de Planta/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Plântula/enzimologia , Plântula/genética , Plântula/fisiologia , Estresse Fisiológico , Transcriptoma , Regulação para CimaRESUMO
Despite continuous improvements in delivery systems, the development of methods for efficient and specific delivery of targeted therapeutic agents still remains an issue in biological treatments such as protein and gene therapy. The endocytic pathway is the major uptake mechanism of cells and any biological agents, such as DNA, siRNA and proteins. These agents become entrapped in endosomes and are degraded by specific enzymes in the lysosome. Thus, a limiting step in achieving an effective biological based therapy is to facilitate the endosomal escape and ensure cytosolic delivery of the therapeutics. Bacteria and viruses are pathogens which use different mechanisms to penetrate the membranes of their target cells and escape the endosomal pathway. Different mechanisms such as pore formation in the endosomal membrane, pH-buffering effect of protonable groups and fusion into the lipid bilayer of endosomes have been proposed to facilitate the endosomal escape. Several viral and bacterial proteins have been identified that are involved in this process. In addition, chemical agents and photochemical methods to rupture the endosomal membrane have been described. New synthetic biomimetic peptides and polymers with high efficacy in facilitating the endosomal escape, low pathogenicity and toxicity have been developed. Each strategy has different characteristics and challenges for designing the best agents and techniques to facilitate the endosomal escape are ongoing. In this review, several mechanisms and agents which are involved in endosomal escape are introduced.
