Dual role of the mitochondrial chaperone Mdj1p in inheritance of mitochondrial DNA in yeast

Mdj1p, a homolog of the bacterial DnaJ chaperone protein, plays an essentia l role in the biogenesis of functional mitochondria in the yeast Saccharomy ces cerevisiae. We analyzed the role of Mdj1p in the inheritance of mitocho ndrial DNA (mtDNA). Mitochondrial genomes were rapidly lost in a temperatur e-sensitive mdj1 mutant under nonpermissive conditions. The activity of mtD NA polymerase was severely reduced in the absence of functional Mdj1p at a nonpermissive temperature, demonstrating the dependence of the enzyme on Md j1p. At a permissive temperature, the activity of mtDNA polymerase was not affected by the absence of Mdj1p. However, under these conditions, intact [ rho(+)] genomes were rapidly converted to nonfunctional [rho(-)] genomes wh ich were stably propagated in an mdj1 deletion strain. We propose that mtDN A polymerase depends on Mdj1p as a chaperone in order to acquire and/or mai ntain an active conformation at an elevated temperature, In addition, Mdj1p is required for the inheritance of intact mitochondrial genomes at a tempe rature supporting optimal growth; this second function appears to be unrela ted to the function of Mdj1p in maintaining mtDNA polymerase activity.