Mitochondrial dynamics: regulatory mechanisms and emerging role in renal pathophysiology

Abstract

Mitochondria are a class of dynamic organelles that constantly undergo fission and fusion. Mitochondrial dynamics is governed by a complex molecular machinery and finely tuned by regulatory proteins. During cell injury or stress, the dynamics is shifted to fission, resulting in mitochondrial fragmentation, which contributes to mitochondrial damage and consequent cell injury and death. Emerging evidence has suggested a role of mitochondrial fragmentation in the pathogenesis of renal diseases including acute kidney injury and diabetic nephropathy. A better understanding of the regulation of mitochondrial dynamics and its pathogenic changes may unveil novel therapeutic strategies.

Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study

“…[24][25][26][27] Mitochondrial dysfunction can weaken a cell's capacity to respond to a range of metabolic processes, including additional oxidative stress and fatty acid overload, and can contribute to progressive disease. 3,28 A transgenic mouse model has shown that mitochondrial dysfunction in podocytes induced by TGF-b signaling preceded the manifestation of segmental glomerulosclerosis. 29 In addition, diabetic mouse models and in vitro studies have demonstrated that hyperglycemia induced mitochondrial fragmentation in podocytes, endothelial cells, and renal tubular cells.…”

“…First, mitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of CKD [3][4][5] and proposed as a therapeutic target for atherosclerotic renovascular disease. 8,17 Mitochondrial dysfunction can be a consequence of oxidative stress.…”

“…Recently, mitochondrial dysfunction in podocytes and kidney tubular cells has been implicated in the pathogenesis of CKD. [3][4][5] Molecules that target mitochondrial function, including thiazolidinediones, have been proposed as therapeutic agents for protecting kidney function. [6][7][8][9] However, studies on measures of mitochondrial dysfunction and CKD at the population level have been limited.…”

“…3 mtDNA copy number has been used as a surrogate measure of mitochondrial function because mitochondrial integrity is difficult to measure. 10 In populationbased studies, higher mtDNA copy number in peripheral blood has been associated with lower risk of mortality.…”

Sphingosine 1-Phosphate Receptor-1 Enhances Mitochondrial Function and Reduces Cisplatin-Induced Tubule Injury

“…Disruption of either fission or fusion can contribute to mitochondrial dysfunction. 40 Hence, there has been considerable interest in targeting mitochondria to improve or maintain mitochondrial stability and prevent tissue damage. 41 Our findings on mitochondrial respiratory function and ultrastructure in S1P1-overexpressing TKPTS cells suggest that S1P1 could be a suitable target for maintaining mitochondrial integrity in kidney tubule cells.…”