Table 1.
Mitochondrial regulatory factors studied in cultured podocytes
| Gene | In Vitro Model | Effects | Mitochondrial Health | Reference |
|---|---|---|---|---|
| PGC-1α | Human podocytes | PGC-1α expression increased with differentiation | ↔ | (41) |
| PGC-1α | Human podocytes treated with HG | Reduced expression of PGC-1α and TFAM | ↓ | (41) |
| PGC-1α | Overexpression of PGC-1α in mouse podocytes | Increase in mitochondrial biogenesis and function; induction of podocyte proliferation and dedifferentiation | ↑ | (49) |
| PGC-1α | Mouse podocytes treated with ADR | Podocyte injury and mitochondrial dysfunction; decreased PGC-1α expression | ↓ | (92) |
| PGC-1α | Overexpression of PGC-1α in mouse podocytes treated with ADR | Protective against podocyte injury and mitochondrial dysfunction | ↑ | (92) |
| PGC-1α | Knockdown of PGC-1α in human podocytes | Reduced mitochondrial function and improved glycolysis | ↓ | (8) |
| SIRT1 | Knockdown of Sirt1 in human podocytes with HG | Reduced expression of PGC-1α, NRF-1, and Tfam; decreased mtDNA | ↓ | (39) |
| TUG1 | Knockout of Tug1 in mouse podocytes treated with HG | Increased mitochondrial ROS and apoptosis; reduced complex I and III activity; reduced ATP | ↓ | (57) |
| TUG1 | Overexpression of Tug1 in mouse podocytes treated with HG | Restored complex I and III activity and ATP level | ↑ | (57) |
| TUG1 | Primary mouse podocytes from db/db Tug1PodTg mice | Increased mitochondrial content and ATP level compared with db/db mice | ↑ | (57) |
| KLF6 | Knockdown and overexpression of KLF6 in ADR-treated mouse and human podocytes | Knockdown of KLF6 in podocytes increased mitochondrial fragmentation and apoptosis; overexpression of KLF6 was able to rescue these changes | ↓ ↑ |
(60) |
| KLF6 | HIV-1-infected human podocytes | Reduced KLF6 expression | ↓ | (60) |
| SCO2 | Knockdown of SCO2 in human podocytes | Increased caspase-9 and release of cytochrome c from mitochondria | ↓ | (60) |
| KLF6 | Knockout and overexpression of KLF6 in human podocytes under HG conditions | Knockout of KLF6 caused mitochondrial injury and apoptosis that was rescued by overexpression of KLF6 | ↓ | (40) |
| TFAM | Knockout of TFAM in human podocytes | Reduced mitochondrial function and increased glycolysis | ↓ | (8) |
| DRP1 | Knockout of DRP1 in human podocytes | No significant change in mitochondrial or glycolytic function | ↔ | (8) |
| DRP1 | Primary podocytes from db/db;Drp1fl/fl mice | Increase in basal and maximal OCR; increased ATP levels | ↑ | (4) |
| DRP1 | Cultured mouse podocyte with Drp1 deletion under HG conditions | Reversed the effect on HG; increased OCR; increased ATP content; reduced ROS production | ↑ | (4) |
| DRP1 | Cultured mouse podocyte with Drp1 knockdown treated with aldosterone | Suppressed mitochondrial fission; attenuated mitochondrial dysfunction and podocyte injury | ↑ | (86) |
| ROCK1 | Knockout of ROCK1 in mouse podocytes treated with HG | Maintained elongated mitochondria; reduced Drp1 recruitment | ↑ | (80) |
ADR, adriamycin; DRP1, dynamin-related protein-1; HG, high glucose; HIV-1, human immunodeficiency virus-1; KLF6, Krüppel-like factor 6; NRF-1, nuclear respiratory factor 1; 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; TFAM, mitochondrial transcription factor A; TUG1, taurine-upregulated gene 1.