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.