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Paediatric Laboratory Medicine

Complex IV

Clinical Significance

To determine the rate of cytochrome C oxidation in mitochondria as a result of cytochrome C oxidase (mitochondrial complex IV, COX) activity.

Test Name

Complex IV

Alternate Name/ Synonym

  • Cytochrome Oxidase (COX)

Gene Name

  • Caused by mutations in nuclear genes and mitochondrial genes

Alternate Gene Name

Cytochrome Oxidase (COX)


Mitochondrial Disease


Spectrophotometric Measurements at 550nm

Turn Around Time

  • Fibroblasts: 3 weeks - 3 months
  • Tissue Biopsies: Fresh - 5 business days
  • Tissue Biopsies: Frozen - 1 month


Various phenotypic forms of COX deficiency have been recognized, the major varieties involving the degeneration of the brain stem and basal ganglia (Leigh syndrome) and lactic acidemia with or without cardiomyopathy.

Specimen Type

  • Endocardial biopsy
  • Fibroblast (CVS/Amnios) extract
  • Fibroblast mitochondria
  • Muscle mitochondria
  • Kidney, liver and muscle homogenates

Minimum Specimen Requirements

  • 1 dish for subculturing
  • 20 dishes for mitochondrial isolation from fibroblasts
  • 30-50 mg from muscle biopsy/autopsy for testing on muscle homogenate
  • 250-300 mg for mitochondrial isolation from fresh muscle biopsy

Optimal Collection Time

  • For fibroblasts, frozen biopsies: anytime
  • Fresh biopsy: until 2:30 pm,  Monday-Friday


  • For fibroblasts: Room temperature
  • Frozen biopsy: transport on dry ice
  • For fresh muscle biopsy: transport from Pathology in dish on ice

Special Requirements

For fresh biopsy: call to book (ext. 205989) at least 24 hours in advance for full Mitochondrial Enzyme screening on isolated mitochondria. Pick up from Pathology.

Shipping and Contact Information

The Hospital for Sick Children
Rapid Response Laboratory
170 Elizabeth Street, Room 3642
Toronto, ON
M5G 2G3
Phone: 416-813-7200
Phone: 1-855-381-3212

Reference Range

  • Fibroblast lysates: 3.51-12.55 nmol/mg/min
  • Fibroblast mitochondria: 22.11-92.01 nmol/mg/min, CIV/CS: 0.37-1.74
  • Muscle homogenate: 0.74-3.91 µmol/min/g wet wt, CIV/CS: ≥0.1
  • Muscle mitochondria: 183.59-821.86 nmol/mg/min, CIV/CS: ≥0.2
  • Kidney homogenate: 0.23-0.84 µmol/min/g wet wt      
  • Liver homogenate: 0.54-2.06 µmol/min/g wet wt
  • Endocardial homogenate: 74.73-268.41 nmol/mg/min

All rates reported in combination with CS rates.


Human COX is a multisubunit assembly in the inner mitochondrial membrane responsible for the terminal event in electron transport in which molecular oxygen is reduced.