Shaping Up Mitochondria in Diabetic Nephropathy

Abstract

Mitochondrial medicine has experienced significant progress in recent years and is expected to grow significantly in the near future, yielding many opportunities to translate novel bench discoveries into clinical medicine. Multiple lines of evidence have linked mitochondrial dysfunction to a variety of metabolic diseases, including diabetic nephropathy (DN). Mitochondrial dysfunction presumably precedes the emergence of key histologic and biochemical features of DN, which provides the rationale to explore mitochondrial fitness as a novel therapeutic target in patients with DN. Ultimately, the success of mitochondrial medicine is dependent on a better understanding of the underlying biology of mitochondrial fitness and function. To this end, recent advances in mitochondrial biology have led to new understandings of the potential effect of mitochondrial dysfunction in a myriad of human pathologies. We have proposed that molecular mechanisms that modulate mitochondrial dynamics contribute to the alterations of mitochondrial fitness and progression of DN. In this comprehensive review, we highlight the possible effects of mitochondrial dysfunction in DN, with the hope that targeting specific mitochondrial signaling pathways may lead to the development of new drugs that mitigate DN progression. We will outline potential tools to improve mitochondrial fitness in DN as a novel therapeutic strategy. These emerging views suggest that the modulation of mitochondrial fitness could serve as a key target in ameliorating progression of kidney disease in patients with diabetes.

Podocyte Bioenergetics in the Development of Diabetic Nephropathy: The Role of Mitochondria

“…Overall, there is a consensus that enhancing mitochondrial biogenesis in podocytes in the diabetic milieu is beneficial for renal function ( 64 , 65 ). Interestingly, thiazolidinediones are PGC-1α activators ( 59 ).…”

Mitochondrial Regulation of Diabetic Kidney Disease

“…The time course of mitochondrial dysfunction in the kidney has been documented in several experimental models of diabetic kidney disease (DKD) ( 6 , 7 ). For instance, it was found that mitochondrial changes in size and function preceded histological and biochemical changes associated with kidney damage and these mitochondrial changes evolved with DKD progression ( 6 ).…”

“…As the most important physiological system for producing chemical energy stored as ATP from glucose, it is not surprising that mitochondria gained early attention as a possible target of diabetes and its micro/macrovascular complications. The time course of mitochondrial dysfunction in the kidney has been documented in several experimental models of diabetic kidney disease (DKD) (6,7). For instance, it was found that mitochondrial changes in size and function preceded histological and biochemical changes associated with kidney damage and these mitochondrial changes evolved with DKD progression (6).…”

NAD metabolism modulates inflammation and mitochondria function in diabetic kidney disease

“…Inflammation and mitochondrial dysfunction are increasingly recognized as important causes of renal diseases [13][14][15][16][17][18] . Kidney is the organ with the second highest oxygen consumption in our body; it is distinctly sensitive to mitochondrial dysfunction, which promotes kidney injury and inflammation 19,20 .…”