SELECTIVE INDUCTION OF MITOCHONDRIAL CHAPERONES IN RESPONSE TO LOSS OF THE MITOCHONDRIAL GENOME

Molecular chaperones are known to play key roles in the synthesis, tra nsport and folding of nuclear-encoded mitochondrial proteins and of pr oteins encoded by mitochondrial DNA. Although the regulation of heat-s hock genes has been the subject of considerable investigation, regulat ion of the genes encoding mitochondrial chaperones is not well defined . We have found that stress applied specifically to the mitochondria o f mammalian cells is capable of eliciting an organelle-specific, molec ular chaperone response. Using the loss of mitochondrial DNA as a mean s of producing a specific mitochondrial stress, we show by Western-blo t analysis that mtDNA-less (rho(0)) rat hepatoma cells show an increas e in the steady-state levels of chaperonin 60 (cpn 60) and chaperonin 10 (cpn 10). Nuclear transcription assays show that the: upregulation of these chaperones is due to transcriptional activation, There was no effect on the inducible cytosolic Hsp 70, Hsp 72, nor on mtHsp 70 in rho(0) cells, leading us to concluded that stress applied selectively to mitochondria elicits a specific molecular chaperone response, Heat stress was able to provide an additional induction of cpn 60 and cpn 1 0 above that obtained for the rho(0) state alone, indicating that thes e genes have separate regulatory elements for the specific mitochondri al and general stress responses. Since the mitochondrial-specific chap erones are encoded by nuclear DNA, there must be a mechanism for molec ular communication between the mitochondrion and nucleus and this syst em can address how stress is communicated between these organelles.