Human mitochondrial complex I is the first enzyme of the mitochondrial respiratory chain. Complex I is composed of 45 subunits, seven encoded by mitochondrial DNA, while the remainder are encoded by nuclear DNA. All nuclear-encoded subunits are thought to be expressed as a single isoform. Here we reveal subunit NDUFV3 to be present in both the canonical 10 kDa and a novel 50 kDa isoform, generated through alternative splicing. Both isoforms assemble into complex I and their levels vary in different tissues. While the 50 kDa isoform appears to be dominant in HEK293T cells, we find either isoform alone is sufficient for assembly of mature complex I. NDUFV3 represents the first known complex I subunit present in two functional isoforms.
Keywords: OXPHOS; NADH dehydrogenase; complex I; metabolism; mitochondria.
© 2016 Federation of European Biochemical Societies.