Centrosomal Memory

The centrosome, classically defined as the primary microtubule-organizing center of the animal cell, is here reconceptualized as a critical organelle for non-genomic cellular memory. We propose the Centrosomal Ledger hypothesis, which posits that the mother centriole encodes a high-dimensional molecular state vector. This distributed memory integrates proteomic composition, post-translational modification (PTM) landscapes, and macromolecular stoichiometries accumulated over a cell’s history. Rather than being a passive structural hub, the centrosome actively utilizes this integrated record to guide future cell fate decisions, such as the choice between symmetric and asymmetric division. Crucically, this hypothesis is untestable by traditional bulk-cell molecular biology, as it requires the discrimination of centriole-age-specific molecular signatures. Its rigorous falsification necessitates centrosome-resolved, multi-omic approaches. Furthermore, we argue that dysregulation of this ledger—through corruption or erosion—constitutes a fundamental mechanistic axis underlying oncogenic transformation, where fate instruction is scrambled, and age-associated stem cell decline, where instructive fidelity is lost. This reframing of the centrosome from a cytoskeletal architect to an information-processing device opens novel translational avenues for diagnosing and treating cancer and degenerative diseases by targeting organelle memory.