PMC6554557_01
Telomeres and kidney disease. Copyright disclosure: mouse: https://commons.wikimedia.org/wiki/File:Vector_diagram_of_laboratory_mouse_%28black_and_white%29.svg; https://creativecommons.org/licenses/by-sa/4.0/deed.en; attribution, "By Gwilz [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], from Wikimedia Commons. Kidney: https://commons.wikimedia.org/wiki/File:Kidney_Cross_Section.png; By Artwork by Holly Fischer [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons.
fgene-10-00453-g001.jpg
PMC6554557_01_fgene-10-00453-g001.jpg
F1
Shorter telomere length has been associated with multi-system diseases, early life stressors, increasing chronological age and all-cause mortality (Figure 1).
Increased mutation rate in mtDNA have previously been associated with several diseases including various forms of kidney disease. These mutations include point mutations, deletions and single nucleotide polymorphisms. Some of these mutations may result in several pathological phenotypes and these have been highlighted by a solid line between such genes.
fgene-10-00453-g002.jpg
PMC6554557_01_fgene-10-00453-g002.jpg
F2
Increased levels of mtDNA mutations have previously been associated with several disorders including various forms of kidney disease (Figure 2). Genetic variation in mtDNA (Figure 2) or nuclear genes (Figure 3) which influence mitochondrial function may impair respiratory chain complex activities leading to an increase in production of ROS resulting in a negative feedback loop, increasing mitochondrial dysfunction, OXPHOS defects and ROS generation along with a reduction in ATP production which leads to increased oxidative stress which may lead to uncontrolled autophagy, mitophagy, and further ROS production.
Genetic variation or altered expression of nuclear genes which encode mitochondrial proteins may impair respiratory chain complex activities leading to an increase in production of reactive oxygen species (ROS). This initiates a negative feedback loop, further reducing mitochondrial function, and ATP production along with an increase in OXPHOS defects and ROS generation leading to increased oxidative stress which may lead to uncontrolled autophagy, mitophagy and further ROS production. Mitochondrial dysfunction, ROS generation and the resulting dysregulation of autophagic mechanisms may also activate intrinsic apoptotic mechanisms resulting in inflammation and fibrosis in the renal tubules, glomerulus and podocytes eventually leading to kidney disease. Red arrows indicate underexpression and green arrows overexpression.
fgene-10-00453-g003.jpg
PMC6554557_01_fgene-10-00453-g003.jpg
F3
Genetic variation in mtDNA (Figure 2) or nuclear genes (Figure 3) which influence mitochondrial function may impair respiratory chain complex activities leading to an increase in production of ROS resulting in a negative feedback loop, increasing mitochondrial dysfunction, OXPHOS defects and ROS generation along with a reduction in ATP production which leads to increased oxidative stress which may lead to uncontrolled autophagy, mitophagy, and further ROS production.