Mitochondrial dysfunction in diabetic kidney disease.
Authors Forbes JM, Thorburn DR
Submitted By Josephine Forbes on 3/27/2018
Status Published
Journal Nature reviews. Nephrology
Year 2018
Date Published 2/1/2018
Volume : Pages Not Specified : Not Specified
PubMed Reference 29456246
Abstract Globally, diabetes is the leading cause of chronic kidney disease and end-stage
renal disease, which are major risk factors for cardiovascular disease and
death. Despite this burden, the factors that precipitate the development and
progression of diabetic kidney disease (DKD) remain to be fully elucidated.
Mitochondrial dysfunction is associated with kidney disease in nondiabetic
contexts, and increasing evidence suggests that dysfunctional renal mitochondria
are pathological mediators of DKD. These complex organelles have a broad range
of functions, including the generation of ATP. The kidneys are mitochondrially
rich, highly metabolic organs that require vast amounts of ATP for their normal
function. The delivery of metabolic substrates for ATP production, such as fatty
acids and oxygen, is altered by diabetes. Changes in metabolic fuel sources in
diabetes to meet ATP demands result in increased oxygen consumption, which
contributes to renal hypoxia. Inherited factors including mutations in genes
that impact mitochondrial function and/or substrate delivery may also be
important risk factors for DKD. Hence, we postulate that the diabetic milieu and
inherited factors that underlie abnormalities in mitochondrial function
synergistically drive the development and progression of DKD.