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General Information
mitochondrial complex V disorders, MT-ATP6-related
FlyBase ID

A number of mitochondrial diseases are associated with defects in the human mitochondrial ATP synthase, MT-ATP6 (OMIM: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; OMIM:256000), neuropathy, ataxia, and retinitis pigmentosa (FBhh0000386; OMIM:551500), myopathy, lactic acidosis, and sideroblastic anemia 3 (FBhh0000379; OMIM:500011), and striatonigral degeneration, infantile, mitochondrial (FBhh0000380; OMIM: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]

Disease Summary Information
Disease Summary: mitochondrial complex V disorders, MT-ATP6-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Cellular phenotype and pathology
Molecular information

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. []

External links
Disease synonyms
mitochondrial complex V (ATP synthetase) disorders, mitochondrial type
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 2 human to 1 Drosophila; the additional orthologous human gene is MT-ATP8.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      mitochondrial ATPase subunit 6 (mt:ATPase6) encodes a mitochondrial inner transmembrane protein that is key for oxidative phosphorylation. It couples hydrogen ion transport to ATP synthesis functioning as part of the ATP synthase. [Date last reviewed: 2019-03-14]
      Gene Groups / Pathways
      Comments on ortholog(s)

      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.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (0 groups)
        Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)
        Models Based on Experimental Evidence ( 1 )
        Modifiers Based on Experimental Evidence ( 1 )
        Alleles Representing Disease-Implicated Variants
        Genetic Tools, Stocks and Reagents
        Sources of Stocks
        Contact lab of origin for a reagent not available from a public stock center.
        Selected mammalian transgenes
        Publicly Available Stocks
        Selected Drosophila transgenes
        Publicly Available Stocks
        RNAi constructs available
        Publicly Available Stocks
        Selected Drosophila classical alleles
        Allele class
        Publicly Available Stocks
        References (13)