mtHsp70 converts mitochondrial proteostasis distress into impaired protein import
Functional mitochondria are essential for cell viability and depend on protein import from the cytosol. Impaired protein import initiates various well-characterized cellular programs that rescue or remove dysfunctional mitochondria. However, the molecular mechanism that underlies the initial reduction of protein import into defective mitochondria remained unknown. Here, we found that the redistribution of mtHsp70, mitochondrial chaperone that is involved in both protein import and protein folding, regulates the efficiency of protein import. During early mitochondrial stress, before rescue programs are initiated and membrane potential is affected, mtHsp70-dependent import was specifically impaired and association of mtHsp70 with the import complex reduced. Even under non-stress conditions, the majority of mtHsp70 is found in a substrate-bound state. We propose that the availability of free mtHsp70 limits protein import into mitochondria during stress.