Expression Profiles of Kidney Mitochondrial Proteome during the Progression of the Unilateral Ureteral Obstruction: Focus on Energy Metabolism Adaptions

Abstract

Kidney diseases encompass many pathologies, including obstructive nephropathy (ON), a common clinical condition caused by different etiologies such as urolithiasis, prostatic hyperplasia in males, tumors, congenital stenosis, and others. Unilateral ureteral obstruction (UUO) in rodents is an experimental model widely used to explore the pathophysiology of ON, replicating vascular alterations, tubular atrophy, inflammation, and fibrosis development. In addition, due to the kidney’s high energetic demand, mitochondrial function has gained great attention, as morphological and functional alterations have been demonstrated in kidney diseases. Here we explore the kidney mitochondrial proteome differences during a time course of 7, 14, and 21 days after the UUO in rats, revealing changes in proteins involved in three main metabolic pathways, oxidative phosphorylation (OXPHOS), the tricarboxylic acid cycle (TCA), and the fatty acid (FA) metabolism, all of them related to bioenergetics. Our results provide new insight into the mechanisms involved in metabolic adaptations triggered by the alterations in kidney mitochondrial proteome during the ON.

Epigenetic regulation of mitochondrial‐endoplasmic reticulum dynamics in kidney diseases

“…Whereas dynamin‐related protein 1 (Drp1) and mitochondrial fission 1 (FIS1) carry out mitochondrial fission (Prinz, 2014). In normal conditions this process is well balanced, however, during pathophysiological conditions, the dynamics resort toward the fission process, thus creating small mitochondrial spheres regarded as mitochondrial fragmentation followed by cell death (Ortega‐Lozano et al, 2022). On the other hand, mitochondria also stimulate reactive oxygen species (ROS) as a by‐product of energy production and metabolism.…”