Krebs Cycle Moonlights in Caspase Regulation Adi Minis, Hermann Steller  Developmental Cell  Volume 37, Issue 1, Pages 1-2 (April 2016) DOI: 10.1016/j.devcel.2016.03.016 Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 1 Spatially Restricted Caspase Activation at the Mitochondrial Membrane during Sperm Differentiation (A) The non-lethal activity apoptotic effector caspases is regulated by multiple pathways at the mitochondrial surface. First, Cytochrome C is necessary to promote caspase activation. Second, the pseudosubstrate Soti and A-Sβt, a testis-specific isoform of the Krebs cycle enzyme Succinyl-CoA synthase β, have antagonistic effects on the activity of a Culin-3-based ubiquitin ligase (CRL3) complex. Activation of CRL3 promotes degradation of the caspase-inhibitor dBruce, which in turn restricts the potentially lethal activity of caspases in time and space. The interplay between Soti and A-Sβt achieves spatial and temporal restriction of caspase activity that is necessary for the selective destruction of subcellular structures during sperm terminal differentiation. (B) Soti and A-Sβt regulate CRL3 to promote caspase activation. Soti inhibits CRL3 by blocking substrate binding. Upon the onset of sperm differentiation, A-Sβt levels increase on the mitochondrial outer membrane (MOM) and compete with Soti for binding to CRL3. This allows for spatially restricted activation of CRL3 at the MOM, which in turn promotes degradation of dBruce and caspase activation. Developmental Cell 2016 37, 1-2DOI: (10.1016/j.devcel.2016.03.016) Copyright © 2016 Elsevier Inc. Terms and Conditions