Blackout in the powerhouse: clinical phenotypes associated with defects in the assembly of OXPHOS complexes and the mitoribosome

Abstract

Mitochondria produce the bulk of the energy used by almost all eukaryotic cells through oxidative phosphorylation (OXPHOS) which occurs on the four complexes of the respiratory chain and the F1-F0 ATPase. Mitochondrial diseases are a heterogenous group of conditions affecting OXPHOS, either directly through mutation of genes encoding subunits of OXPHOS complexes, or indirectly through mutations in genes encoding proteins supporting this process. These include proteins that promote assembly of the OXPHOS complexes, the post-translational modification of subunits, insertion of cofactors or indeed subunit synthesis. The latter is important for all 13 of the proteins encoded by human mitochondri..