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FB2026_01
,
released March 12, 2026
A number of mitochondrial diseases are associated with defects in the human mitochondrial ATP synthase, MT-ATP6 (MIM:516060; see Allelic Variants section or table). There is a single fly ortholog, Dmel\mt:ATPase6, for which a loss-of-function mutation and RNAi-targeting constructs have been generated.
The human MT-ATP6 gene has not been introduced into flies. Specific diseases associated with MT-ATP6 include Leigh syndrome, MT-ATP6-related (FBhh0000387; MIM:256000), neuropathy, ataxia, and retinitis pigmentosa (FBhh0000386; MIM:551500), myopathy, lactic acidosis, and sideroblastic anemia 3 (FBhh0000379; MIM:500011), and striatonigral degeneration, infantile, mitochondrial (FBhh0000380; MIM:500003).
One of the phenotypes described for Dmel\mt:ATPase6 is bang-sensitivity (FBcv:0000391), a phenotype similar to seizure sensitivity in humans; see the human disease model report for epilepsy (FBhh0000268). Several other fly genes characterized as models of mitochondrial disease also exhibit bang-sensitive phenotypes, including sesB (see mitochondrial myopathy, SLC25A4(ANT1)-related, FBhh0000372), mt:ND2 (see mitochondrial complex I deficiency, MT-ND2-related, FBhh0000382), and Ttc19 (see mitochondrial complex III deficiency, nuclear type 2, FBhh0000369).
Adult flies homozygous for a loss-of-function Dmel\mt:ATPase6 allele show bang sensitivity, reduced locomotor activity, and reduced lifespan. Progressive, adult-onset neuromuscular dysfunction and myodegeneration is observed; micrographs reveal abnormal appearance of mitochondria. A single genetic interaction (with sesB) is described; see the gene report for mt:ATPase6.
[updated Aug. 2016 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]
Some mitochondrial disorders affect a single organ (eye or ear, for example), but most involve multiple organ systems and often present with prominent neurologic and myopathic features. [Gene Reviews, Primary Mitochondrial Disorders Overview]
Mitochondrial complex V (ATP synthase) effects the final step of oxidative phosphorylation in the mitochondrial respiratory chain.
Complex V (ATP synthase) 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]
Many to one: 2 human to 1 Drosophila; the additional orthologous human gene is MT-ATP8.
Moderate-scoring ortholog of human mitochondrial gene MT-ATP6; lower-scoring ortholog of human MT-ATP8 (1 Drosophila to 2 human). Dmel\mt:ATPase6 shares 56% identity and 38% similarity with human MT-ATP6.