Disorders of ATP synthase, the key enzyme in mitochondrial energy supply, belong to the most severe metabolic diseases, manifesting as early-onset mitochondrial encephalo-cardiomyopathies. Since ATP synthase subunits are encoded by both mitochondrial and nuclear DNA, pathogenic variants can be found in either genome. In addition, the biogenesis of ATP synthase requires several assembly factors, some of which are also hotspots for pathogenic variants. While variants of MT-ATP6 and TMEM70 represent the most common cases of mitochondrial and nuclear DNA mutations respectively, the advent of next-generation sequencing has revealed new pathogenic variants in a number of structural genes and TMEM70, sometimes with truly peculiar genetics. Here we present a systematic review of the reported cases and discuss biochemical mechanisms, through which they are affecting ATP synthase. We explore how the knowledge of pathophysiology can improve our understanding of enzyme biogenesis and function. Keywords: Mitochondrial diseases o ATP synthase o Nuclear DNA o Mitochondrial DNA o TMEM70.

• MeSH
• fenotyp * MeSH
• lidé MeSH
• membránové proteiny genetika   metabolismus   MeSH
• mitochondriální DNA genetika   MeSH
• mitochondriální nemoci genetika   enzymologie   MeSH
• mitochondriální proteiny genetika   metabolismus   MeSH
• mitochondriální protonové ATPasy * genetika   metabolismus   MeSH
• mitochondrie enzymologie   genetika   MeSH
• mutace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH
• Názvy látek
• membránové proteiny MeSH
• mitochondriální DNA MeSH
• mitochondriální proteiny MeSH
• mitochondriální protonové ATPasy * MeSH
• TMEM70 protein, human MeSH Prohlížeč