ABSTRACT
We show that TANGO2 in mammalian cells localizes predominantly to mitochondria and partially at mitochondria sites juxtaposed to lipid droplets (LDs) and the endoplasmic reticulum. HepG2 cells and fibroblasts of patients lacking TANGO2 exhibit enlarged LDs. Quantitative lipidomics revealed a marked increase in lysophosphatidic acid (LPA) and a concomitant decrease in its biosynthetic precursor phosphatidic acid (PA). These changes were exacerbated in nutrient-starved cells. Based on our data, we suggest that TANGO2 function is linked to acyl-CoA metabolism, which is necessary for the acylation of LPA to generate PA. The defect in acyl-CoA availability impacts the metabolism of many other fatty acids, generates high levels of reactive oxygen species, and promotes lipid peroxidation. We suggest that the increased size of LDs is a combination of enrichment in peroxidized lipids and a defect in their catabolism. Our findings help explain the physiological consequence of mutations in TANGO2 that induce acute metabolic crises, including rhabdomyolysis, cardiomyopathy, and cardiac arrhythmias, often leading to fatality upon starvation and stress.
Subject(s)
Fatty Acids , Lipid Metabolism , Animals , Humans , Endoplasmic Reticulum/metabolism , Fatty Acids/metabolism , Fibroblasts/metabolism , Homeostasis , Lipid Droplets/metabolism , Lipid Metabolism/physiology , Mammals/metabolism , Mitochondrial Proteins/metabolism , Vesicular Transport Proteins/metabolismABSTRACT
En noviembre 2014 la Sociedad Española de Otorrinolaringología, la Sociedad Española de Sueño y la Sociedad Española de Cirugía Maxilofacial propusieron y avalaron la elaboración de una Guía de Práctica Clínica sobre la exploración física de la vía aérea superior en pacientes con apnea obstructiva del sueño. La Guía ha seguido de forma estricta en toda su elaboración las recomendaciones del manual de elaboración de guías de práctica clínica del Sistema Nacional de Salud 2007 y 2009 y el manual de la Scottish Intercollegiate Guidelines Network (SIGN) 2015. El documento final puede ser altamente útil para los fines que se propuso inicialmente: ser un referente para unificar las regiones que deben ser exploradas en los pacientes con síndrome de apnea-hipoapnea obstructiva del sueño, mediante qué tipo de exploración y cómo gradarla, y expresada para todos los ámbitos asistenciales a los que estos pacientes pueden acudir. Las conclusiones y recomendaciones están basadas en una revisión exhaustiva y actualizada de la bibliografía con alto nivel de evidencia, además de la experiencia y conocimientos demostrados de todos los integrantes del grupo de elaboración. Dicho grupo se constituyó pensando siempre en la transversalidad del proyecto, y, por tanto, han participado especialistas de todos los ámbitos implicados (cirugía maxilofacial, medicina de familia, neumología, neurofisiología clínica, odontología y otorrinolaringología). Con la misma idea se seleccionaron los revisores externos del texto final
In November 2014 the Spanish Society of Otolaryngology, the Spanish Sleep Society and the Spanish Society of Maxillofacial Surgery proposed and endorsed the development of a Clinical Practice Guideline on the physical examination of the upper airway in patients with obstructive sleep apnoea. The Guideline strictly followed the recommendations of the manual for the preparation of clinical practice guidelines of the National Health System 2007 and 2009 and the manual of the Scottish Intercollegiate Guidelines Network (SIGN) 2015. The final document could be highly useful for the purposes that were originally proposed: to act as a reference to unify the regions that should be explored in patients with obstructive sleep apnoea-hypopnoea syndrome, the type of examination and how to grade it, and specific to all the care areas to which these patients have access. The conclusions and recommendations are based on a thorough and up-to-date review of the literature with a high level of evidence, as well as the experience and knowledge demonstrated by all the members of the drafting group. This group was formed bearing in mind at all times the transversality of the project, and, therefore, specialists from all the involved areas participated (maxillofacial surgery, family medicine, pneumology, clinical neurophysiology, odontology and otolaryngology). The external reviewers of the final text were selected along the same lines
Subject(s)
Humans , Sleep Apnea Syndromes/diagnosis , Sleep Apnea Syndromes/therapy , Airway Management/standards , Physical Examination/methods , Societies, Medical/standards , Physical Examination/standardsABSTRACT
In November 2014 the Spanish Society of Otolaryngology, the Spanish Sleep Society and the Spanish Society of Maxillofacial Surgery proposed and endorsed the development of a Clinical Practice Guideline on the physical examination of the upper airway in patients with obstructive sleep apnoea. The Guideline strictly followed the recommendations of the manual for the preparation of clinical practice guidelines of the National Health System 2007 and 2009 and the manual of the Scottish Intercollegiate Guidelines Network (SIGN) 2015. The final document could be highly useful for the purposes that were originally proposed: to act as a reference to unify the regions that should be explored in patients with obstructive sleep apnoea-hypopnoea syndrome, the type of examination and how to grade it, and specific to all the care areas to which these patients have access. The conclusions and recommendations are based on a thorough and up-to-date review of the literature with a high level of evidence, as well as the experience and knowledge demonstrated by all the members of the drafting group. This group was formed bearing in mind at all times the transversality of the project, and, therefore, specialists from all the involved areas participated (maxillofacial surgery, family medicine, pneumology, clinical neurophysiology, odontology and otolaryngology). The external reviewers of the final text were selected along the same lines.
