Abstract
Disruption of mitochondrial biosynthesis or dynamics, or loss of control over mitochondrial regulation leads to a significant alteration in fuel preference and metabolic shifts that potentially affect the health of kidney cells. Mitochondria regulate metabolic networks which affect multiple cellular processes. Indeed, mitochondria have established themselves as therapeutic targets in several diseases. The importance of mitochondria in regulating the pathogenesis of several diseases has been recognized, however, there is limited understanding of mitochondrial biology in the kidney. This review provides an overview of mitochondrial dysfunction in kidney diseases. We describe the importance of mitochondria and mitochondrial sirtuins in the regulation of renal metabolic shifts in diverse cells types, and review this loss of control leads to increased cell-to-cell transdifferentiation processes and myofibroblast-metabolic shifts, which affect the pathophysiology of several kidney diseases. In addition, we examine mitochondrial-targeted therapeutic agents that offer potential leads in combating kidney diseases.
Highlights
Chronic kidney disease (CKD), which affects 10–15% of people, is a leading cause of death worldwide (Levin et al, 2017)
Renal fibrosis is the final consequence of all types of progressive kidney disease, including diabetic kidney disease (DKD), that results in end-stage renal disease (ESRD) (Allison, 2019; Cooper and Warren, 2019)
Renal fibrosis results in damage to normal cellular functions and structures and is a result of severe inflammation and loss of control over wound healing mechanisms which lead to an excess accumulation of extracellular matrix (ECM) and fibrosis-associated proteins (Srivastava et al, 2019b)
Summary
Disruption of mitochondrial biosynthesis or dynamics, or loss of control over mitochondrial regulation leads to a significant alteration in fuel preference and metabolic shifts that potentially affect the health of kidney cells. Mitochondria have established themselves as therapeutic targets in several diseases. The importance of mitochondria in regulating the pathogenesis of several diseases has been recognized, there is limited understanding of mitochondrial biology in the kidney. This review provides an overview of mitochondrial dysfunction in kidney diseases. We describe the importance of mitochondria and mitochondrial sirtuins in the regulation of renal metabolic shifts in diverse cells types, and review this loss of control leads to increased cell-to-cell transdifferentiation processes and myofibroblast-metabolic shifts, which affect the pathophysiology of several kidney diseases. We examine mitochondrial-targeted therapeutic agents that offer potential leads in combating kidney diseases
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