Potential mechanisms for the cellular consequences of ribosomal haploinsufficiency. (A) Top panel: Normal cell in unstressed conditions, with unperturbed ribosome biogenesis and steady levels of p53. Bottom panel: Ribosomal haploinsufficiency leads to up-regulation of rpL11, which binds to MDM2 causing p53 activation, which results in apoptosis and cell-cycle arrest. (B) Top panel: Normal hemoglobin synthesis, with the coordinated production of heme and globin. Bottom panel: Relative excess of free heme leads to oxidative stress and hemolysis through a variety of mechanisms.⁷³