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J Pathol. 2018 Nov;246(3):261-265. doi: 10.1002/path.5146. Epub 2018 Sep 25.

Multilevel heterogeneity of mitochondrial respiratory chain deficiency.

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Wellcome Centre for Mitochondrial Research and Centre for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK.
Department of Psychiatry, Division of Behavioral Medicine, Columbia University Medical Center, New York, New York, USA.
Department of Neurology and Columbia Translational Neuroscience Initiative, H. Houston Merritt Center, Columbia University Medical Center, New York, New York, USA.
Columbia University Aging Center, Columbia University, New York, New York, USA.


Mitochondrial diseases are heterogeneous multisystem disorders that show a mosaic pattern of mitochondrial respiratory chain dysfunction. The mitochondrial DNA (mtDNA) mutation load is heterogeneous at multiple levels: across organs, between cells, and between subcellular compartments. Such heterogeneity poses a diagnostic challenge, but also provides a scientific opportunity to explore the biological mechanisms underlying the onset and progression of these disorders. A recent article in The Journal of Pathology described a novel histochemical technique - nitro blue tetrazolium exclusion assay (NBTx) - to quantify mitochondrial cytochrome c oxidase (COX, or complex IV) deficiency. This technique is rapid, cost-effective, and quantitative, and is more sensitive than previous histochemical methods. It can also be applied across model organisms and human tissues. The NBTx method should therefore be a useful diagnostic tool, and may catalyze research examining the cellular and subcellular mechanisms that drive the onset and progression of inherited and acquired mtDNA disorders. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


COX deficiency; NBTx; biochemical; biopsy; cytochrome c oxidase; genetic; histochemistry; mitochondrial disease; mitochondrial disorder; skeletal muscle; subcellular


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