Neuropediatrics 2008; 39 - V27
DOI: 10.1055/s-0029-1215740

Relevance of functional investigations of the mitochondrial energy metabolism in unfrozen tissue

J Mayr 1, J Koch 1, C Rauscher 1, P Freisinger 2, B Rolinski 3, U Ahting 3, W Sperl 1
  • 1Paracelsus Medizinische Privatuniversität Salzburg, Universitätsklinik für Kinder- und Jugendheilkunde, Salzburg, Austria
  • 2Kinderklinik und Poliklinik der TU München, München, Germany
  • 3Klinikum München-Schwabing, Institut für Klinische Chemie, München, Germany

The mitochondrial energy metabolism consists of numerous enzymatic reactions and transport processes. Especially transport processes depend on functionally intact mitochondrial membranes and can only be investigated in unfrozen tissue. However mitochondrial diagnostics is based in many diagnostic centres solely on morphologic investigations or biochemical investigations of frozen tissue.

In our laboratory 403 unfrozen muscle biopsies have been investigated by respirometry and/or radiochemical substrate oxidation analysis. In 76 of these patients a defect within the mitochondrial energy metabolism has been identified. 52 patients had a deficiency of the respiratory chain, 15 a defect of the pyruvate oxidation and 9 of the ATP synthesis (1). 6 patients with a defect in the ATP synthesis had a diminished content of the F1F0 ATP synthase in Blue Native polyacrlyamide electrophoresis, in 5 of these patients we could identify a defect of TMEM70 by reversed genetics (3), a protein which is most likely a novel mitochondrial assembly factor. In 1 patient we found for the first time a defect of the mitochondrial phosphate carrier (3). Measurement of the pyruvate dehydrogenase complex showed normal activities in 3 patients, where pyruvate oxidation was diminished in the functional analysis. This could point to possible, so far undescribed defects of pyruvate import.

Taken together 1/3 of our patients with defects in the mitochondrial energy metabolism had either a deficiency in ATP synthesis or pyruvate oxidation. 25% of these patients had normal activities in isolated enzyme measurements of the mitochondrial energy metabolism from frozen biopsies. Therefore – in our experience – functional investigation of unfrozen mitochondria is necessary for a complete evaluation of patients suspected for a mitochondrial disorder.

(1) Sperl et al. Neuromuscul Disord 16 (2006) 821–9

(2) Cízková et al. Nat Genet 40 (2008) 1288–90

(3) Mayr et al. Am J Hum Genet 80 (2007) 478–84