ClpB, a member of class 1 AAA+ proteins, is a key chaperone with disaggregase activity [1,4,6,7]. It is crucial for bacterial survival under various stress conditions, especially heat shock, and also regulates the secretion of bacterial effector molecules related to type VI secretion systems [1]. In plants, ClpB/Hsp100 proteins are involved in heat stress tolerance by preventing and dissociating protein aggregates [5].

CLPB mutations are associated with 3-methylglutaconic aciduria and neutropenia [2]. In a CLPB-null environment, there is a stress-specific aggregation phenotype, and CLPB deficiency impedes the function of the proteolytic SPY complex due to protein aggregation in the mitochondrial intermembrane space, suggesting an interdependency of mitochondrial quality control components [2]. Also, CLPB preferentially attaches to mitochondrial RNA granules and translation initiation components, indicating its role in counteracting misfolded insoluble protein assemblies that contain nucleotides [3].

In conclusion, ClpB plays essential roles in stress responses in bacteria and plants, and its mitochondrial counterpart CLPB is involved in maintaining the functional integrity of mitochondrial proteolytic complexes. The study of CLPB-related KO models helps understand the molecular mechanisms underlying diseases like 3-methylglutaconic aciduria and neutropenia, providing insights into potential therapeutic strategies.