interesting Aug 2004 mito/biopsy study

[Guest guest]

Thought some of you might be interested in this abstract of a new

report. If diagnosis isn't already complicated enough, this report

suggests that different methods of measuring mito enzyme activity

may produce different results. Even in a patient with a known mtDNA

mutation, one method found normal activity of complexes I-IV while

another found deficiencies. The researchers suggest that it may be

necessary to test both ways to be sure....

Barbara

Med Sci Monit. 2004 Aug 20;10(9):CS49-CS53.

Enzymatic diagnosis of oxidative phosphorylation defects on muscle

biopsy: Better on tissue homogenate or on a mitochondria-enriched

suspension?

Casademont J, Perea M, S, Beato A, Miro O, Cardellach F.

Muscle Research Unit, Department of Internal Medicine, Hospital

Clinic. " August Pi i Sunyer " Biomedical Research Institute

(IDIBAPS). School of Medicine, University of Barcelona. Barcelona,

Spain.

Background: The enzymatic analysis of mitochondrial respiratory

chain (MRC) complexes of skeletal muscle is an important step in the

diagnosis of mitochondrial disorders. Because of its lesser

turbidity and increased sensitivity, mitochondrial fractionation has

been increasingly considered the diagnostic method of choice

compared with the more classical analysis of muscle homogenate. In

circumstances in which mitochondria become abnormal in number, size

or shape, the process of mitochondrial enrichment made by sequential

centrifugation and washing may favor the selection of the most

normal mitochondria, eliminating the most abnormal ones. In this

situation, the study of muscle homogenate, paradoxically, may better

reflect what happens in vivo. Case Report: To exemplify this

situation we present a 60-year-old woman with a complete

mitochondrial phenotype and a 70% heteroplasmic presence of the

mtDNA A3243G mutation in muscle tissue. The respiratory and

enzymatic activities from mitochondria-enriched muscle suspension

were within normal control limits. In contrast, when muscle

homogenate was studied, enzyme activities of complexes I, III, and V

were found to be decreased. Conclusions: Although mitochondria-

enriched muscle suspensions are usually more informative than muscle

homogenates for studies of MRC, in some situations it may be

necessary to study both to uncover the biochemical defect.