Mitochondrial dysfunction and endoplasmic reticulum stress in the promotion of fibrosis in obstructive nephropathy induced by unilateral ureteral obstruction.
Elena Martínez-KlimovaOmar Emiliano Aparicio-TrejoTania Gómez-SierraAlexis Paulina Jiménez-UribeBelen BellidoPedraza-Chaverri JoséPublished in: BioFactors (Oxford, England) (2020)
Obstructive nephropathy favors the progression to chronic kidney disease (CKD), a severe health problem worldwide. The unilateral ureteral obstruction (UUO) model is used to study the development of fibrosis. Impairment of renal mitochondria plays a crucial role in several types of CKD and has been strongly related to fibrosis onset. Nevertheless, in the UUO model, the impairment of mitochondria, their relationship with endoplasmic reticulum (ER) stress induction and the participation of both to induce the fibrotic process remain unclear. In this review, we summarize the current information about mitochondrial bioenergetics, redox dynamics, mitochondrial mass, and biogenesis alterations, as well as the relationship of these mitochondrial alterations with ER stress and their participation in fibrotic processes in UUO models. Early after obstruction, there is metabolic reprogramming related to mitochondrial fatty acid β-oxidation impairment, triggering lipid deposition, oxidative stress, (calcium) Ca2+ dysregulation, and a reduction in mitochondrial mass and biogenesis. Mitochondria and the ER establish a pathological feedback loop that promotes the impairment of both organelles by ER stress pathways and Ca2+ levels dysregulation. Preserving mitochondrial and ER function can prevent or at least delay the fibrotic process and loss of renal function. However, deeper understanding is still necessary for future clinically-useful therapies.
Keyphrases
- oxidative stress
- endoplasmic reticulum
- chronic kidney disease
- endoplasmic reticulum stress
- induced apoptosis
- fatty acid
- systemic sclerosis
- cell death
- healthcare
- public health
- end stage renal disease
- physical activity
- ischemia reperfusion injury
- transcription factor
- hydrogen peroxide
- mental health
- protein kinase
- current status
- editorial comment