Molecular chaperones cooperate with PIM1 protease in the degradation of misfolded proteins in mitochondria

ATP dependent proteolytic degradation of misfolded proteins in the
mitochondrial matrix is mediated by the PIM1 protease and depends
on the molecular chaperone proteins mt-hsp70 and Mdj1p. Chaperone
function is essential to maintain misfolded proteins in a soluble
state, a prerequisite for their degradation by PIM1 protease. In
the absence of functional mt-hsp70 or Mdj1p misfolded proteins
either remain associated with mt-hsp70 or form aggregates and
thereby are no longer substrates for PIM1 protease. Mdj1p is shown
to regulate the ATP dependent association of an unfolded
polypeptide chain with mt-hsp70 affecting binding to as well as
release from mt-hsp70. These findings establish a central role of
molecular chaperone proteins in the degradation of misfolded
proteins by PIM1 protease and thereby demonstrate a functional
interrelation between components of the folding machinery and the
proteolytic system within mitochondria.