Alterations in Mitochondrial Oxidative Phosphorylation System: Relationship of Complex V and Cardiac Dysfunction in Human Heart Failure

Autores de IIS La Fe

• Isaac Giménez Escamilla

  Autor

• Carlota Benedicto Marrero

  Autor

• Lorena Pérez Carrillo

  Autor

• Marta Delgado Arija

  Autor

• Irene González Torrent

  Autor

• Roger Vílchez Medina

  Autor

• 

  Luis Vicente Martínez Dolz

  Autor

• Manuel Portoles Sanz

  Autor

• Estefanía Tarazón Melguizo

  Autor

• 

  Esther Roselló Lletí

  Autor

Grupos

• Grupo de Investigación Clínica y Traslacional en Cardiología

• Patología Neuromuscular y Ataxias

Abstract

Heart failure (HF) is a disease related to bioenergetic mitochondrial abnormalities. However, the whole status of molecules involved in the oxidative phosphorylation system (OXPHOS) is unknown. Therefore, we analyzed the OXPHOS transcriptome of human cardiac tissue by RNA-seq analyses (mRNA n = 36; ncRNA n = 30) in HF patients (ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM)) and control subjects. We detected 28 altered genes in these patients, highlighting greater deregulation in ICM. Specifically, we found a general overexpression of complex V (ATP synthase) elements, among them, ATP5I (ICM, FC = 2.04; p < 0.01), ATP5MJ (ICM, FC = 1.33, p < 0.05), and ATP5IF1 (ICM, FC = 1.81; p < 0.001), which presented a significant correlation with established echocardiographic parameters of cardiac remodeling and ventricular function as follows: left ventricular end-systolic (p < 0.01) and end-diastolic (p < 0.01) diameters, and ejection fraction (p < 0.05). We also detected an increase in ATP5IF1 protein levels (ICM, FC = 1.75; p < 0.01) and alterations in the microRNA expression levels of miR-208b-3p (ICM, FC = -1.44, p < 0.001), miR-483-3p (ICM, FC = 1.37, p < 0.01), regulators of ATP5I. Therefore, we observed the deregulation of the OXPHOS transcriptome in ICM patients, highlighting the overexpression of complex V and its relationship with cardiac remodeling and function.

Keywords

• mitochondria; heart failure; ischemic and dilated cardiomyopathy; OXPHOS; complex V; cardiac remodeling