The Centriolar Satellite Component CEP131 timely regulates mitochondrial Apoptosis

Centriolar satellites are multiprotein aggregates that orbit the centrosome and govern centrosome homeostasis and primary cilia formation. In contrast to the scaffold PCM1, which nucleates centriolar satellites and has been linked to microtubule dynamics, autophagy, and intracellular trafficking, the functions of its close interactant CEP131 beyond ciliogenesis remain unclear. By using a knockout strategy in a T-cell line unable to form primary cilia, we report that, although dispensable for centriolar satellite assembly, CEP131 participates in optimal tubulin modifications and microtubule regrowth. Our unsupervised label-free proteomic analysis by quantitative mass spectrometry further uncovered both a mitochondrial and an anti-apoptotic signature. Without CEP131, mitochondria showed increased respiration and formed a more elongated network. In response to cell death inducers converging on mitochondria, knockout cells displayed delayed cytochrome c release from mitochondria, subsequent caspases activation, and ultimately in apoptosis. This defect in mitochondrial permeabilization was intrinsic as it could be recapitulated in vitro with isolated organelles. Together, these data extend the functions of CEP131 to life-and-death decisions and propose ways to interfere with mitochondrial apoptosis.