Skd3 (human ClpB) is a potent ATP-dependent mitochondrial protein disaggregase that is activated by the rhomboid protease, PARL, and inactivated by MGCA7-linked mutations.

Protein disaggregases employ two mechanically-linked ATPase rings that are under steric control by a wrapped-around coiled-coil belt.

Exploring natural Hsp104 variation reveals unexpected tuning of a passive activity that inhibits aggregation of specific substrates to selectively counter TDP-43 or alpha-synuclein proteotoxicity connected to neurodegenerative disease.

The bacterial AAA+ chaperone ClpL recognizes aggregated proteins via multiple contacts of its unique N-terminal domain and refolds them with high efficiency providing superior heat resistance.

The emergence of complementary electrostatic potentials after the prokaryotic-to-eukaryotic split drives physical and functional cooperation between canonical class A and class B J-proteins to boost protein disaggregation.

A comparison in yeast and human cells reveals a remarkable variability in the properties of RNP granules and highlights a key role for protein disaggregation machines in regulating RNP granule assembly.

Hsp70 chaperone provides Hsp104 with high efficiency in disaggregation and specificity towards aggregated substrates at the, otherwise limiting, cellular concentrations of adenine nucleotides.

The aging lineage of budding yeast is differentiated by an early-appearing protein deposit that promotes protein quality control.

Development of sequential mixing, single turnover stopped-flow approach reveals processive protein unfolding catalyzed by Escherichia coli ClpB.

Recovery of proteins from aggregates by Hsp70 is boosted by the Hsp110 co-chaperone, which promotes abundant Hsp70 recruitment to aggregates and supports initial aggregate remodelling into small assemblies.