SOD4 is critical for fungal virulence, particularly under iron-limited host conditions:
Iron Starvation Response: Transcriptionally regulated by the iron-responsive factor SEF1, SOD4 is upregulated during iron deprivation to mitigate oxidative stress .
Hyphal Morphogenesis: While SOD5 is induced during hyphal growth, SOD4 expression remains independent of morphological changes, instead focusing on iron homeostasis .
Host Immune Evasion: By neutralizing extracellular superoxide, SOD4 protects fungal cells from oxidative bursts generated by immune cells .
Prokaryotic Systems: E. coli yields SOD4 with and , comparable to eukaryotic systems like Pichia pastoris .
Post-Translational Modifications: Unlike native SOD4, recombinant versions lack glycosylation, affecting thermal stability (half-life of 15 minutes at 90°C) .
Recombinant SOD4 has been explored in gene therapy models for cardiovascular and neurological protection:
Myocardial Stunning: Adenovirus-mediated delivery of SOD4 reduced infarct size by 50% in rabbits by targeting extracellular superoxide at the sarcolemma .
Neuroprotection: Intracranial gene transfer in rabbits increased cerebrospinal fluid SOD activity by 148 U/mL, enhancing resistance to ischemic stroke .
SOD4 activity is tightly controlled by environmental cues:
Transcriptional Regulation:
Post-Translational Modulation:
| Parameter | SOD4 | EC-SOD (SOD3) | Cu/Zn-SOD (SOD1) |
|---|---|---|---|
| Localization | Cell wall/extracellular | Extracellular matrix | Cytoplasm |
| Metal Dependency | Cu-only | Cu/Zn | Cu/Zn |
| Pathogen Association | Candida virulence | Mammalian antioxidant defense | Ubiquitous cellular defense |
| Therapeutic Half-Life | 20 hours (plasma) | 6–8 hours (plasma) | 7 minutes (plasma) |
STRING: 6239.F55H2.1b
UniGene: Cel.19659