Mitochondrial Complex IV Deficiency

DNA code analysis

In previous posts we looked at a review by Dose J, Huebbe P, Nebel A and Rimbach G titled  ‘APOE4 genotype and stress response – a mini review’. Dose and colleagues noted evidence that APOE4 binds to mitochondrial complexes III and IV.

 I looked at ‘mitochondrial complex IV deficiency’ in medline. However a search using the term ‘cytochrome c oxidase (COX) deficiency’ produced more results.

There was one paper by Abdulhag and colleagues, reporting on a mitochondrial complex IV deficiency. There were a number of salient features of the case
(1) This affected the brain, skeletal muscle and heart
(2) This manifested during the neurodevelopmental period
(3) There was Occipital and subcortical involvement

(4) Hydrocephalus

The authors report on other findings described elsewhere with different mutations with variation in phenotype. This aspect of the report suggests that the exact nature of the mutation may be critical in understanding the phenotype and may limit the generalisations that can be drawn.

With that caveat, in Alzheimer’s Disease according to Small and Duff’s Dual Pathway Hypothesis, APOE4 will impact on Tau and Amyloid production. The pathway would be considered brain specific. In this case there is cardiac and skeletal muscle involvement. The pathology is also subcortical and Occipital. Again (as in the case of Mitochondrial Complex III deficiency) the correlates would not be typical of those reported with Alzheimer’s Disease and Alzheimer’s Type Dementia.

The complicating factors are that the two pathologies are being described at different points in the lifespan and are distinct in their localisation.


Abdulhag UN, Soiferman D, Schueler-Furman O, et al. Mitochondrial complex IV deficiency, caused by mutated COX6B1, is associated with encephalomyopathy, hydrocephalus and cardiomyopathy. European Journal of Human Genetics. 2015;23(2):159-164. doi:10.1038/ejhg.2014.85.

Dose J, Huebbe P, Nebel A, Rimbach G. APOE genotype and stress response – a mini review. Lipids in Health and Disease. 2016;15:121. doi:10.1186/s12944-016-0288-2.

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