FEBS Letters accepted
Mitochondria are sometimes referred to as the ‘powerhouses of the cell’ because they are the organelles housing the main energy transducing system, responsible for ATP synthesis through the process of oxidative phosphorylation (OXPHOS). Dysfunction of this system leads to a group of heterogeneous syndromes that are generically known as ‘mitochondrial diseases’, which constitute the majority of inborn errors of metabolism. A large proportion of these disorders are associated with pathological variants in genes, located in both the mitochondrial and nuclear genomes, encoding either structural subunits of the OXPHOS complexes or accessory factors necessary for their correct assembly or functionality. This article reviews and updates our current knowledge of the genetic defects, molecular mechanisms and clinical phenotypes found in this class of mitochondrial diseases.
The biogenesis of the OXPHOS system relies on structural components encoded both in the mitochondrial genome (mtDNA) and in the nucleus. All the assembly factors are encoded in the nuclear genome, synthesized in the cytoplasm and imported inside the mitochondria, where they coordinate the assembly of the subunits coming from inside and outside the organelle. Mutations in the genes encoding a large number of these elements have been determined as the cause of mitochondrial disease. The figure depicts the organization of the human respiratory chain in which the practical totality of complex I (cI) is associated in supercomplexes (SC) I1III2 and the respirasomes I1III2IV1.
First published: 30 March 2021