Mitochondria and chronic kidney disease: a molecular update

Chronic kidney disease (CKD) has become a worldwide public health priority and is estimated to affect approximately 12% of the global population. CKD is associated with an increased cardiovascular morbidity, premature mortality, and a substantial economic burden.

Increased generation of reactive oxygen species has been observed throughout CKD progression, suggesting that mitochondrial dysfunction may be important in the pathogenesis of kidney disease. The mitochondrial genome is a circular double stranded DNA molecule composed of 16,569 base pairs harbouring 37 genes, which encode 13 key proteins of the electron transport chain along with two rRNAs and 22 tRNAs. At least 2,309 nuclear genes are also necessary for efficient mitochondrial function. Mitochondrial dysfunction leads to a reduction in ATP production, cellular damage and loss of renal function. Damage or mutations in mtDNA will lead to defects in mitochondrial oxidative phosphorylation (OXPHOS), which can result in a range of clinical symptoms involving several different organs broadly termed as ‘mitochondrial diseases’. Defects in nuclear encoded genes may also lead to OXPHOS defects, abnormal protein translation and loss of mtDNA copy number.

This review provides an update on molecular features influencing mitochondrial homeostasis and function, highlighting how these are compromised during CKD.