RTN4IP1 is essential for the final stages of mitochondrial complex I assembly

A biochemical deficiency of mitochondrial complex I (CI) underlies ~30% of cases of primary mitochondrial disease, yet the inventory of molecular machinery required for CI assembly remains incomplete. We previously characterised patients with isolated CI deficiency caused by segregating variants in RTN4IP1, encoding a poorly characterised mitochondrial protein. Here, we used MS-complexome profiling to characterise the functional consequences of RTN4IP1 deficiency in both patient-derived fibroblasts and U2OS-knockout cells, demonstrating that RTN4IP1 is a bona fide CI assembly factor.