Disorders from perturbations of nuclear‐mitochondrial intergenomic cross‐talk

In the course of evolution, mitochondria lost their independence, and mitochondrial DNA (mtDNA) became the 'slave' of nuclear DNA, depending on numerous nucleus-encoded factors for its integrity, replication and expression. Mutations in any of these factors may alter the cross-talk between the two genomes and cause Mendelian disorders characterized by qualitative (multiple deletions) or quantitative (depletion) alterations of mtDNA, or by defective translation of mtDNA-encoded respiratory chain components.