Multilevel heterogeneity of mitochondrial respiratory chain deficiency

Abstract

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.