CISD3 is a mitochondrial iron-sulfur protein containing two [2Fe-2S] clusters that functions as a critical regulator of cellular energy metabolism and redox homeostasis 1. Primary function: CISD3 transfers its iron-sulfur clusters to electron transport chain components, particularly complex I subunit NDUFV2, supporting oxidative phosphorylation and mitochondrial ATP production 1. The protein maintains mitochondrial iron homeostasis and regulates reactive oxygen species levels essential for normal mitochondrial function 2. Mechanism: CISD3 exists predominantly in a reduced state in cells and undergoes redox-dependent conformational changes at its C-terminal CDGSH domain that facilitate cooperative electron transfer 2. The protein is sensitive to nitric oxide exposure, which causes cluster disassembly and protein destabilization 2. Disease relevance: CISD3 deficiency causes skeletal muscle atrophy with proteomic features resembling Duchenne muscular dystrophy and impairs complex I function 1. Conversely, elevated CISD3 in cancers promotes tumor progression, while CISD3 overexpression induces ferroptosis and reduces cancer cell proliferation 34. CISD3 dysfunction is implicated in alcoholic liver disease through dysregulated copper metabolism and mitochondrial dysfunction 5. Clinical significance: CISD3 emerges as both a prognostic biomarker and potential therapeutic target across multiple pathologies, from muscle degeneration and age-related diseases to cancer and metabolic disorders 13.