EXPRESSION OF STRESS PROTEINS AND MITOCHONDRIAL CHAPERONINS IN CHRONICALLY STIMULATED SKELETAL-MUSCLE

Molecular chaperones and cytosolic stress proteins are actively involv ed in the stabilization, import and refolding of precursor proteins in to mitochondria. The purpose of the present study was to evaluate the relationship between mitochondrial content under steady-state conditio ns, and during the induction of organelle biogenesis, with the express ion of stress proteins and mitochondrial chaperonins. A comparison of steady-state levels of mitochondrial enzyme activity [cytochrome c oxi dase (CYTOX)] with chaperonin levels [the heat-shock protein HSP60, th e glucose-regulated protein GRP75 (mtHSP70)] in striated muscles posse ssing a wide range of oxidative capacities revealed a proportional exp ression between the two. This relationship was disrupted by chronic co ntractile activity brought about by 10 days of 10 Hz stimulation of th e tibialis anterior (TA) muscle, which induced 2.4-fold increases in C YTOX activity, but 3.2-and 9.3-fold increases in HSP60 and GRP75 respe ctively. The inducible stress protein HSP70(i) was detected at low lev els in control TA muscle, and was increased 9.6-fold by chronic contra ctile activity, to values comparable with those found in the unstresse d soleus muscle. This increase occurred in the absence of changes in t ype I MHC levels, indicating independent regulation of these genes. De spite the increases in HSP60 and HSP70(i) proteins, contractile activi ty did not alter their respective mRNA levels, illustrating post-trans criptional mechanisms of gene regulation during contractile activity. In contrast, the mRNA levels encoding the co-chaperonin CPN10 were inc reased 3.3-fold by contractile activity. Thus, the expression of indiv idual mitochondrial chaperonins is independently regulated and uncoord inated. The extent of the induction of these stress proteins and chape ronins by contractile activity exceeded that of membrane enzymes (e.g. CYTOX). It remains to be determined whether this marked induction of proteins comprising part of the protein import machinery is beneficial for the translocation of enzyme precursors into the mitochondria duri ng conditions of accelerated biogenesis.