This report describes general characteristics of the group of diseases classified as mitochondrial complex V (ATP synthase) deficiency, nuclear type (MC5DN). MC5DN is a genetically heterogeneous disorder, with multiple genes and mapped loci. A comprehensive list of MC5DN subtypes, as defined by OMIM, can be found by following the link in the "OMIM phenotypic series" section, below, or by viewing the table below, with links to more detailed reports for subtypes that have been investigated using fly models.
Mitochondrial complex V (ATP synthase) effects the final step of oxidative phosphorylation in the mitochondrial respiratory chain. The mammalian enzyme comprises 17 subunits encoded by nuclear DNA and 2 subunits (MT-ATP6 and MT-ATP8) encoded by mtDNA.
[updated Apr. 2019 by FlyBase; FBrf0222196]
Leigh syndrome may be a feature of a deficiency of any of the mitochondrial respiratory chain complexes, including complex V deficiency.
Mitochondrial complex V deficiency can cause a wide variety of signs and symptoms affecting many organs and systems of the body, particularly the nervous system and the heart. The disorder can be life-threatening in infancy or early childhood. Affected individuals may have feeding problems, slow growth, low muscle tone (hypotonia), extreme fatigue (lethargy), and developmental delay. They tend to develop elevated levels of lactic acid in the blood (lactic acidosis), which can cause nausea, vomiting, weakness, and rapid breathing. High levels of ammonia in the blood (hyperammonemia) can also occur in affected individuals, and in some cases result in abnormal brain function (encephalopathy) and damage to other organs. Other common features are hypertrophic cardiomyopathy and a characteristic pattern of facial features. [from Genetics Home Reference, Mitochondrial complex V deficiency; 2020.08.14]
Nuclear types of mitochondrial complex V deficiency include MC5DN1, caused by mutation in the ATPAF2 gene; MC5DN2, caused by mutation in the TMEM70 gene; MC5DN3, caused by mutation in the ATP5E gene; and MC5DN4, caused by mutation in the ATP5A1 gene. Mutations in the mitochondrial-encoded MT-ATP6 -and MT-ATP8 genes can also cause mitochondrial complex V deficiency. [from MIM:604273; 2016.08.25]
Mitochondrial complex V (ATP synthase) effects the final step of oxidative phosphorylation in the mitochondrial respiratory chain.
Complex V of the mitochondrion comprises 17 subunits encoded by nuclear DNA and 2 subunits (MT-ATP6 and MT-ATP8) encoded by mtDNA. [http://www.genenames.org/cgi-bin/genefamilies/set/644]
