Human Disease Model Report: mitochondrial complex IV dysfunction, general model

General Information

Name

mitochondrial complex IV dysfunction, general model

FlyBase ID

FBhh0001034

Disease Ontology Term

cytochrome-c oxidase deficiency disease

Parent Disease

OMIM

Overview

Mutations in Drosophila genes that encode components of mitochondrial complex IV (also known as cytochrome c oxidase or COX) have been used to model general dysfunction of this essential enzyme of the mitochondrial respiratory chain.

Fly genes used include COX4, COX5A, COX5B, COX7A, and cype (ortholog of COX6C).

This system has been used to assess the ability of alternative oxidases (AOX) from lower eukaryotes to rescue loss-of-function phenotypes of Drosophila COX component genes.

[updated May 2019 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: mitochondrial complex IV dysfunction, general model

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

External links

MedlinePlus (condition): Cytochrome c oxidase deficiency
KEGG Disease Pathways: Oxidative phosphorylation

Disease synonyms

COX dysfunction

cytochrome c oxidase dysfunction

Related Diseases

Related human health report(s)

mitochondrial complex IV deficiency, nuclear type

Ortholog Information

Human gene(s) in FlyBase

Other mammalian ortholog(s) used

Cint\AOX

D. melanogaster Gene Information (5)

Dmel\COX4

Gene Snapshot

Cytochrome c oxidase subunit 4 (COX4) encodes a subunit of the cytochrome-c oxidase. It is involved in cell proliferation and golgi structural organisation. [Date last reviewed: 2019-09-12]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human COX4I1 and COX4I2.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\COX5A

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human COX5A.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\COX5B

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human COX5B.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\COX7A

Gene Snapshot

Contributions welcome

Molecular function (GO)

protein-macromolecule adaptor activity

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Moderate-scoring ortholog of human COX7A1, COX7A2, and COX7A2L.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\cype

Gene Snapshot

cyclope (cype) encodes a cytochrome c oxidase subunit VIc homolog acting as an enhancer of dpp pathway phenotypes. It is involved in hair and cell growth and in ommatidia development. [Date last reviewed: 2019-03-07]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Moderate-scoring ortholog of human COX6C.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (86 groups)

COX4

RNA-protein

Interacting group

Assay

References

COX4 - clu

anti bait coimmunoprecipitation, reverse transcription pcr

(Sen and Cox, 2022)

protein-protein

Interacting group

Assay

References

COX4 - Adh

experimental knowledge based

(Guruharsha et al., 2011)

COX4 - ATPsynCF6

experimental knowledge based

(Guruharsha et al., 2011)

COX4 - ATPsynF

experimental knowledge based

(Guruharsha et al., 2011)

COX4 - ATPsynO

experimental knowledge based

(Guruharsha et al., 2011)

COX4 - CG13887

experimental knowledge based

(Guruharsha et al., 2011)

COX4 - COX5A

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022, Rahman et al., 2014)

COX4 - COX5B

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX4 - COX6B

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022, Rahman et al., 2014)

COX4 - COX7A

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX4 - COX7AL2

experimental knowledge based, cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022, Guruharsha et al., 2011)

COX4 - COX7B

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX4 - COX8

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX4 - cype

blue native page, peptide massfingerprinting, cosedimentation

(Brischigliaro et al., 2022, Rahman et al., 2014)

COX4 - Gpdh1

experimental knowledge based

(Guruharsha et al., 2011)

COX4 - GstS1

experimental knowledge based

(Guruharsha et al., 2011)

COX4 - levy

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022, Rahman et al., 2014)

COX4 - Mlc1

experimental knowledge based

(Guruharsha et al., 2011)

COX4 - Mlc2

experimental knowledge based

(Guruharsha et al., 2011)

COX4 - mt:CoI

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022, Rahman et al., 2014)

COX4 - mt:CoII

cosedimentation, blue native page, peptide massfingerprinting, experimental knowledge based

(Brischigliaro et al., 2022, Rahman et al., 2014, Guruharsha et al., 2011)

COX4 - mt:CoIII

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX4 - ND-MLRQ

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX4 - Ost48

experimental knowledge based

(Guruharsha et al., 2011)

COX4 - Phb1

experimental knowledge based

(Guruharsha et al., 2011)

COX4 - porin

experimental knowledge based

(Guruharsha et al., 2011)

COX4 - Rab1

experimental knowledge based

(Guruharsha et al., 2011)

COX4 - Tm2

experimental knowledge based

(Guruharsha et al., 2011)

COX4 - Tspo

experimental knowledge based

(Guruharsha et al., 2011)

COX4 - UQCR-C2

experimental knowledge based

(Guruharsha et al., 2011)

COX5A

protein-protein

Interacting group

Assay

References

COX5A - ATPsynF

experimental knowledge based

(Guruharsha et al., 2011)

COX5A - CG5174

experimental knowledge based

(Guruharsha et al., 2011)

COX5A - CG32700

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

COX5A - COX4

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022, Rahman et al., 2014)

COX5A - COX5B

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5A - COX6B

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022, Rahman et al., 2014)

COX5A - COX7A

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5A - COX7AL2

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5A - COX7B

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5A - COX8

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5A - cype

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022, Rahman et al., 2014)

COX5A - Cyt-c1

experimental knowledge based

(Guruharsha et al., 2011)

COX5A - fln

experimental knowledge based

(Guruharsha et al., 2011)

COX5A - GstS1

experimental knowledge based

(Guruharsha et al., 2011)

COX5A - levy

blue native page, peptide massfingerprinting, cosedimentation

(Brischigliaro et al., 2022, Rahman et al., 2014)

COX5A - mt:CoI

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022, Rahman et al., 2014)

COX5A - mt:CoII

blue native page, peptide massfingerprinting, cosedimentation

(Brischigliaro et al., 2022, Rahman et al., 2014)

COX5A - mt:CoIII

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5A - ND-MLRQ

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5A - TpnC4

experimental knowledge based

(Guruharsha et al., 2011)

COX5B

protein-protein

Interacting group

Assay

References

COX5B - CG14710

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

COX5B - COX4

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5B - COX5A

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5B - COX6B

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5B - COX7A

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5B - COX7AL2

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5B - COX7B

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5B - COX8

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5B - cype

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5B - Eip75B

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

COX5B - KFase

experimental knowledge based

(Guruharsha et al., 2011)

COX5B - levy

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5B - mt:CoI

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5B - mt:CoII

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5B - mt:CoIII

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5B - ND-MLRQ

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX5B - Pfdn1

experimental knowledge based

(Guruharsha et al., 2011)

COX5B - rdx

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

COX5B - ValRS-m

experimental knowledge based

(Guruharsha et al., 2011)

COX7A

protein-protein

Interacting group

Assay

References

COX7A - COX4

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX7A - COX5A

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX7A - COX5B

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX7A - COX6B

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX7A - COX7AL2

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX7A - COX7B

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX7A - COX8

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX7A - cype

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX7A - levy

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX7A - mt:CoI

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX7A - mt:CoII

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX7A - mt:CoIII

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

COX7A - ND-MLRQ

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

RNA-protein

Interacting group

Assay

References

COX7A - smg

anti bait coimmunoprecipitation, primer specific pcr

(Chartier et al., 2015)

cype

protein-protein

Interacting group

Assay

References

cype - COX4

blue native page, peptide massfingerprinting, cosedimentation

(Brischigliaro et al., 2022, Rahman et al., 2014)

cype - COX5A

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022, Rahman et al., 2014)

cype - COX5B

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

cype - COX6B

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022, Rahman et al., 2014)

cype - COX7A

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

cype - COX7AL2

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

cype - COX7B

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

cype - COX8

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

cype - levy

blue native page, peptide massfingerprinting, cosedimentation

(Brischigliaro et al., 2022, Rahman et al., 2014)

cype - mt:CoI

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022, Rahman et al., 2014)

cype - mt:CoII

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022, Rahman et al., 2014)

cype - mt:CoIII

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

cype - ND-MLRQ

cosedimentation, blue native page, peptide massfingerprinting

(Brischigliaro et al., 2022)

Alleles Reported to Model Human Disease (Disease Ontology) (12 alleles)

COX4

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

COX4^KK107510

model of cytochrome-c oxidase deficiency disease

CEA

(Kemppainen et al., 2014)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

COX4^KK107510

model of cytochrome-c oxidase deficiency disease

is ameliorated by Zzzz\AOX^Scer\UAS.cFa

(Kemppainen et al., 2014)

is ameliorated by Cint\AOX^UAS.cFa

(Kemppainen et al., 2014)

COX5A

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

COX5A^GD5167

model of cytochrome-c oxidase deficiency disease

CEA

(Kemppainen et al., 2014)

Modifiers Based on Experimental Evidence ( 2 )

Allele

Disease

Interaction

References

COX5A^GD5167

model of cytochrome-c oxidase deficiency disease

is ameliorated by Zzzz\AOX^αTub84B.PK

(Kemppainen et al., 2014)

is ameliorated by Cint\AOX^αTub84B.PK

(Kemppainen et al., 2014)

exacerbates cancer

modeled by Wwox^KK108459

(Choo et al., 2015)

COX5A^tend

exacerbates Parkinson's disease 2

modeled by park²⁵

(O'Hanlon et al., 2022)

COX5B

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

COX5B^GD6659

model of cytochrome-c oxidase deficiency disease

CEA

(Kemppainen et al., 2014)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

COX5B^GD6659

model of cytochrome-c oxidase deficiency disease

is ameliorated by Zzzz\AOX^αTub84B.PK

(Kemppainen et al., 2014)

is ameliorated by Zzzz\AOX^Scer\UAS.cFa

(Kemppainen et al., 2014)

is ameliorated by Cint\AOX^αTub84B.PK

(Kemppainen et al., 2014)

is ameliorated by Cint\AOX^UAS.cFa

(Kemppainen et al., 2014)

exacerbates cancer

modeled by Wwox^KK108459

(Choo et al., 2015)

COX7A

Models Based on Experimental Evidence ( 2 )

Allele

Disease

Evidence

References

COX7A^KK110870

model of cytochrome-c oxidase deficiency disease

CEA

(Kemppainen et al., 2014)

COX7A^HMC04889

model of epilepsy

CEA

(Hope et al., 2020)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

COX7A^KK110870

model of cytochrome-c oxidase deficiency disease

is ameliorated by Zzzz\AOX^Scer\UAS.cFa

(Kemppainen et al., 2014)

is ameliorated by Cint\AOX^UAS.cFa

(Kemppainen et al., 2014)

cype

Models Based on Experimental Evidence ( 2 )

Allele

Disease

Evidence

References

cype^GD908

model of cytochrome-c oxidase deficiency disease

CEA

(Kemppainen et al., 2014)

cype^KK111375

model of cytochrome-c oxidase deficiency disease

CEA

(Brischigliaro et al., 2022)

Modifiers Based on Experimental Evidence ( 2 )

Allele

Disease

Interaction

References

cype^GD908

model of cytochrome-c oxidase deficiency disease

is ameliorated by Zzzz\AOX^αTub84B.PK

(Kemppainen et al., 2014)

is ameliorated by Cint\AOX^αTub84B.PK

(Kemppainen et al., 2014)

cype^DP01427

ameliorates Parkinson's disease 2

modeled by park²⁵

(O'Hanlon et al., 2022)

Cint\AOX

Models Based on Experimental Evidence ( 0 )

Allele

Disease

Evidence

References

Modifiers Based on Experimental Evidence ( 3 )

Allele

Disease

Interaction

References

Cint\AOX^αTub84B.PK

ameliorates cytochrome-c oxidase deficiency disease

modeled by COX5A^GD5167

(Kemppainen et al., 2014)

modeled by COX5B^GD6659

(Kemppainen et al., 2014)

modeled by cype^GD908

(Kemppainen et al., 2014)

modeled by levy¹

(Kemppainen et al., 2014)

Cint\AOX^UAS.cFa

DOES NOT ameliorate mitochondrial metabolism disease

modeled by tko^25t

(Kemppainen et al., 2014)

ameliorates Parkinson's disease 7

modeled by dj-1β^GE23381

(Fernandez-Ayala et al., 2009)

ameliorates cytochrome-c oxidase deficiency disease

modeled by COX4^KK107510

(Kemppainen et al., 2014)

modeled by COX5B^GD6659

(Kemppainen et al., 2014)

modeled by COX7A^KK110870

(Kemppainen et al., 2014)

modeled by levy^KK108963

(Kemppainen et al., 2014)

DOES NOT ameliorate autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 3

modeled by mtDNA-helicase^A442P.UAS

(Rodrigues et al., 2018)

modeled by mtDNA-helicase^K388A.UAS

(Rodrigues et al., 2018)

modeled by mtDNA-helicase^KK102418

(Rodrigues et al., 2018)

DOES NOT ameliorate Alpers-Huttenlocher syndrome

modeled by PolG1^KK100485

(Rodrigues et al., 2018)

ameliorates Huntington's disease

modeled by Hsap\HTT^Q93.ex1.UAS

(Campesan et al., 2023)

Cint\AOX^wt.UAS

DOES NOT ameliorate autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 3

modeled by mtDNA-helicase^A442P.UAS

(Rodrigues et al., 2018)

modeled by mtDNA-helicase^K388A.UAS

(Rodrigues et al., 2018)

modeled by mtDNA-helicase^KK102418

(Rodrigues et al., 2018)

DOES NOT ameliorate Alpers-Huttenlocher syndrome

modeled by PolG1^KK100485

(Rodrigues et al., 2018)

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.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

w¹¹¹⁸, P{tub-AOX.K}35; P{tub-AOX.K}112; P{tub-AOX.K}7

w¹¹¹⁸; P{UAS-AOX.F}F6

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

cype^GD908

P{GD908}

w¹¹¹⁸; P{GD908}v13403

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00815}attP2

COX5B^HMC06619

P{TRiP.HMC06619}

y¹ sc^* v¹ sev²¹; P{TRiP.HMC06619}attP40

COX5B^GD6659

P{GD6659}

w¹¹¹⁸; P{GD6659}v30892

w¹¹¹⁸; P{GD1781}v3923

w¹¹¹⁸; P{GD3912}v37496

y¹ sc^* v¹ sev²¹; P{TRiP.HMC04889}attP40

w¹¹¹⁸; P{GD5167}v44490

y¹ v¹; P{TRiP.JF02700}attP2

y¹ v¹; P{TRiP.HMJ22367}attP40/CyO

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

cype^DP01427

y¹ w^67c23; P{Mae-UAS.6.11}cype^DP01427/CyO

COX5A^tend

ethyl methanesulfonate

w^*; P{neoFRT}82B COX5A^tend/TM6B, Tb¹

References (9)

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