Protein quality control and proteolysis. A) Model for cytoplasmic protein quality control in B. subtilis to which cytoplasmic proteins, membrane proteins and secretory proteins are subject. Depending on the presence or absence of targeting signals, newly synthesized proteins can be targeted for secretion or membrane insertion, or they can remain in the cytoplasm. If control of their folding by chaperones is insufficient these proteins can misfold and/or aggregate. This can lead to degradation by proteases such as ClpCP, ClpEP or ClpXP. Alternatively, misfolded proteins can be refolded with the help of chaperones. B) Model for protein quality control and degradation of membrane proteins within the membrane of B. subtilis. Proteins targeted to the membrane can be subject to processing by signal peptidases (e.g. SipS-W) or to degradation by membrane-associated proteases such as FtsH, PrsW, RasP or SpoIVFA. C) Model for extracytoplasmic protein quality control and degradation in B. subtilis. Translocated secretory proteins can fold with the help of folding catalysts such as PrsA. Accumulation of misfolded translocated proteins at the membrane-cell wall interface can trigger a secretion stress response, involving the CssRS two-component regulatory system. If activated, CssRS causes the up regulation of membrane-associated proteases such as HtrA and HtrB. These two proteins can probably catalyze both protein degradation and protein folding. Misfolded proteins are furthermore subject to degradation by cell wall-associated and/or secreted proteases, such as AprE, Bpf, Epr, Mpr, NprB, NprE, Vpr and/or WprA.