Hsp78 chaperone functions in restoration of mitochondrial network following heat stress.

Under physiological conditions mitochondria of yeast Saccharomyces cerevisiae form a branched tubular network, the continuity of which is maintained by balanced membrane fusion and fission processes. Here, we show using mitochondrial matrix targeted green fluorescent protein that exposure of cells to extreme heat shock led to dramatic changes in mitochondrial morphology, as tubular network disintegrated into several fragmented vesicles. Interestingly, this fragmentation did not affect mitochondrial ability to maintain the membrane potential. Cells subjected to recovery at physiological temperature were able to restore the mitochondrial network, as long as an active matrix chaperone, Hsp78, was present. Deletion of HSP78 gene did not affect fragmentation of mitochondria upon heat stress, but significantly inhibited ability to restore mitochondrial network. Changes of mitochondrial morphology correlated with aggregation of mitochondrial proteins. On the other hand, recovery of mitochondrial network correlated with disappearance of protein aggregates and reactivation of enzymatic activity of a model thermo-sensitive protein: mitochondrial DNA polymerase. Since protein disaggregation and refolding is mediated by Hsp78 chaperone collaborating with Hsp70 chaperone system, we postulate that effect of Hsp78 on mitochondrial morphology upon recovery after heat shock is mediated by its ability to restore activity of unknown protein(s) responsible for maintenance of mitochondrial morphology.