Table 2.
Mitochondrial regulator factors studied in murine models of kidney disease
| Gene | Murine Model | Additional Stress | Effects | Mitochondrial Function | Reference |
|---|---|---|---|---|---|
| PGC-1α | Inducible podocyte-specific overexpression of PGC-1α | Induced collapsing FSGS | ↓ | (49) | |
| PGC-1α | Inducible podocyte-specific overexpression of PGC-1α | Diabetes (STZ) | Mice not protected from diabetes-induced albuminuria | ↓ | (49) |
| PGC-1α | Male Sprague-Dawley rats | ADR-induced FSGS | Podocyte mitochondrial dysfunction; increase in ROS and cell apoptosis and decrease in PGC-1α expression | ↓ | (92) |
| PGC-1α | Podocyte-specific knockout of PGC-1α | Reduced mitochondrial biogenesis but no impact on mitochondrial substrate preferences | ↓ | (8) | |
| SIRT1 | Global inducible and reversible Sirt1 knockdown | No significant effect in glomerular function under basal conditions | ↔ | (14) | |
| SIRT1 | Global inducible and reversible Sirt1 knockdown | Diabetes (STZ) | Promotes mitochondrial injury in glomerular cells | ↓ | (14) |
| SIRT1 | Inducible podocyte-specific Sirt1 knockdown | ADR-induced FSGS | Enhanced susceptibility to ADR-induced FSGS; mtDNA damage | ↓ | (14) |
| SIRT1 | Podocyte-specific Sirt1 knockdown | Diabetes (db/db mice) | Increased susceptibility to diabetic nephropathy | ↓ | (55) |
| SIRT1 | Inducible podocyte-specific Sirt1 knockdown | Aging | Aggravated glomerular and podocyte injury; decrease in PGC-1α | ↓ | (13) |
| SIRT1 | Inducible podocyte-specific SIRT1 overexpression | Diabetes (OVE26 mice) | Attenuated DKD progression and podocyte loss | ↑ | (39) |
| TUG1 | Podocyte-specific overexpression of Tug1 | Diabetes (db/db mice) | Attenuated DKD progression; regulates PGC-1α | ↑ | (57) |
| KLF6 | Podocyte-specific knockdown of Klf6 | ADR-induced FSGS | Induced mitochondrial dysfunction; reduced mitochondrial transcripts; reduced ATP levels and OCR | ↓ | (60) |
| KLF6 | Podocyte-specific knockdown of Klf6 | Diabetes (STZ) | Increased susceptibility to diabetic nephropathy; reduced complex IV activity and ATP levels | ↓ | (40) |
| ROCK1 | Global knockout of Rock1 | Diabetes (STZ; db/db mice) | Decrease in albuminuria | ↑ | (80) |
| ROCK1 | Podocyte-specific inducible knockin of constitutively active ROCK1 | Promoted podocyte loss; albuminuria; increase in mtROS and apoptosis | ↓ | (80) | |
| DRP1 | Inducible podocyte-specific Drp1 knockout | Diabetes (db/db mice) | Ameliorates key diabetic nephropathy features and podocytes have elongated mitochondria | ↑ | (4) |
| ROCK1- mediated phosphorylated DRP1 | Global Drp1S600A knockin | Diabetes (db/db mice) | Protective against diabetic nephropathy by preventing recruitment on Drp1 to mitochondria | ↑ | (27) |
| TFAM | Podocyte-specific Tfam knockout | No change in overall podocyte health | ↔ | (8) |
ADR, adriamycin; DKD, diabetic kidney disease; DRP1, dynamin-related protein-1; Drp1S600A, Drp1 serine 600 mutated to alanine; FSGS, focal segmental glomerulosclerosis; KLF6, Krüppel-like factor 6; OCR, oxygen consumption rate; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator-1α; ROCK1, Rho-associated coiled coil-containing protein kinase 1; ROS, reactive oxygen species; SIRT1, sirtuin 1; STZ, streptozotocin; TFAM, mitochondrial transcription factor A; TUG1, taurine-upregulated gene 1.