Iron-sulfur cluster transfer protein NUBPL

NUBPL is an iron-sulfur cluster transfer protein that mediates assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) by delivering iron-sulfur clusters to complex I subunits (UniProt: Q8TB37). The protein is essential for proper mitochondrial oxidative phosphorylation; mutations cause mitochondrial complex I deficiency, nuclear type 21 (MC1DN21), an autosomal recessive disorder with variable presentation ranging from neonatal lethality to adult-onset neurodegeneration, including Leigh syndrome and Parkinson disease phenotypes (UniProt: Q8TB37).

In Alzheimer's disease brain tissue, NUBPL is significantly downregulated compared to age-matched controls, with a mean log2 fold-change of −0.51 (Chaparral AD proteomics). This reduction was detected in post-mortem human AD brain via TMT-labeled tandem mass spectrometry across subcellular fractions. The downregulation suggests compromised mitochondrial Complex I assembly or function in AD pathology, linking energy metabolism dysfunction to neurodegeneration in this context.