Hoppel 2017 MiPschool Obergurgl E1

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Charles Hoppel
The challenges of functional mitochondrial diagnosis.

Link: MitoEAGLE

Hoppel C (2017)

Event: MiPschool Obergurgl 2017

COST Action MitoEAGLE

Mitochondrial functional testing has revolved around the essential role of oxidizing substrates with the production of ATP. Other approaches have included determination of the activities of the individual complexes of the electron transport chain, as well as, linked activity of two of the complexes. The tissue most often used has been skeletal muscle, but skin fibroblasts and blood formed elements have become important sources. While permeabilized skeletal muscle fibers have been used for diagnostic studies, this method is more frequently used as a research tool.

We will review integrated mitochondrial function measured as oxidative phosphorylation using substrates that enter the oxidative system at distinct sites. Most of the data have been generated from skeletal muscle biopsies. We combine function studies with analysis of the individual complexes on both isolated mitochondria and skeletal muscle, add quantitative phospholipid and supercomplex analysis for a comprehensive examination of mitochondria. The challenge in 2017 is that the use functional testing has declined as genomic approaches to diagnosis have increased and have become the dominant method.

While WES has surpassed all other approaches to diagnosis of mitochondrial diseases, there are many mutations for which the pathological and physiological impact are now known. It is this area where functional testing still has a role. Additionally, mutations in genes that are not commonly associated with mitochondrial disease will not be understood without functional testing.


Bioblast editor: Kandolf G O2k-Network Lab: US OH Cleveland Hoppel CL


Labels: MiParea: nDNA;cell genetics, mt-Medicine 


Tissue;cell: Skeletal muscle  Preparation: Isolated mitochondria 



Event: E1, Review 


Affiliations

Center Mitochondrial Diseases, Dept Pharmacol Medicine, Case Western Reserve Univ School Medicine, Cleveland, OH, USA. - charles.hoppel@case.edu