(36) EXPRESSION OF MITOCHONDRIAL STRESS PROTEINS AND OF ENZYMES INVOLVED IN REACTIVE OXYGEN SPECIES METABOLISM IN RESPIRATORY CHAIN DEFICIENCIES

Catherine Godinot (1) and Henri Carrier (2)
(1) Centre de Génétique Moléculaire et Cellulaire, UMR 5534 - CNRS - UCB Lyon I - 69622 Villeurbanne, France
(2) Groupe de Recherches en Pathologie Neuromusculaire. INSERM U499, Faculté de Médecine Laënnec, 12 rue Guillaume Paradin, 69372 LYON Cedex 08, France

The ragged red fibers (RRF) represent a hallmark in most skeletal muscles harbouring a mitochondrial respiratory chain deficiency. They exhibit aggregates of abnormal mitochondria which are located under their subsarcolemma, where the succinate dehydrogenase activity is increased whereas the cytochrome oxidase activity is very often lacking within the fiber. In these RRFs, transcripts of mitochondrial and nuclear genes which encode subunits of oxidative phosphorylation complexes are overexpressed in muscles harbouring mtDNA deletions (Carrier et al, 1996).

Therefore, a mtDNA deletion increases the transcription of respiratory chain complex subunits of nuclear origin as well as it activates succinate dehydrogenase activity. However, this is not a simple general induction of all mitochondrial proteins of nuclear origin. Indeed, the mitochondrial Hsp60 which is essential for processing and refolding the proteins encoded by the nuclear genome that mitochondria import from the cytosol is overexpressed in the intermyofibrillar mitochondria of the RRF but it is not expressed within the subsarcolemmal aggregates, as shown by immunolabeling performed on frozen muscle slices.

The manganese dependent superoxide dismutase (MnSOD) which dismutates the superoxide anions into hydrogen peroxide anions in mitochondria is also overexpressed in the RRF. More precisely, it is strongly expressed within the subsarcolemmal aggregates of these organelles.

Whether this MnSOD overexpression represents a possible defense mechanisms against free radical generation that electron transfer chain impairment induces will be discussed as well as the possible consequences of the lack of Hsp60 in subsarcolemmal abnormal mitochondria and of its overexpression in interfibrillar mitochondria.

Carrier H, Burt-Pichat B, Flocard F, Guffon N, Mousson B, Dumoulin R, Godinot C (1996) Acta Neuropathol 91:104-111.