NDUFA8 is a nuclear-encoded accessory subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), localized to the intermembrane surface where it stabilizes the membrane domain 1. As a non-catalytic component, NDUFA8 does not participate directly in electron transfer but is essential for Complex I assembly and stability 234. NDUFA8 is highly expressed in metabolically active tissues including heart and skeletal muscle 5. Mechanistically, NDUFA8 promotes mitochondrial oxidative phosphorylation and ATP production 6. It stabilizes iron-sulfur (Fe-S) clusters critical for Complex I function and other Fe-S-dependent enzymes like aconitase 7. NDUFA8 supports mitochondrial quality control through circadian regulation of mitophagy in cardiac tissue 8. Biallelic NDUFA8 mutations cause mitochondrial Complex I deficiency with variable clinical severity. Patients exhibit developmental delay, microcephaly, and epilepsy, though rare cases show favorable outcomes 34. NDUFA8 upregulation in cervical cancer promotes proliferation and chemotherapy resistance by enhancing mitochondrial respiration, regulated transcriptionally via EP300/H3K27 acetylation 67. Dysregulation of NDUFA8 expression associates with acute myocardial infarction pathogenesis 9.