Cop1-Drp1 · Exploring the role of mitochondrial dynamics in tumor regulation by Cop1

The Constitutive morphogenetic protein 1 (Cop1) is an E3-ubiquitin ligase regulating stability of a broad group of targets with pleiotropic functions. Cop1 emerged as a tumour suppressor in T-cell lymphomas and in prostate cancer. During tumour formation, mitochondria are key organelles regulating cell death and proliferation. This multiplicity of functions is mirrored by the complex morphology of the organelle, resulting from the equilibrium between fusion and fission, events controlled by a set of mitochondria-shaping proteins. Fission depends on the large GTPase dynamin-related protein 1 (DRP1), essential for embryonic development and involved in the control of apoptosis and cell cycle.We found that loss of Cop1 results in increased cell death, DNA damage, mitochondrial fragmentation, and accumulation of D1, highlighting a potential connection between a tumour suppressor and mitochondrial morphology. We therefore hypothesize that Drp1-mediated regulation of mitochondrial morphology participates in tumour suppression by Cop1. To address this hypothesis, we will verify if (i) Drp1 is epistatic to Cop1 in accumulation of DNA damage and sensitivity to cell death; (ii) Drp1 is required for lymphomagenesis in Cop1h/h mice . Our project is expected to establish the role of mitochondrial morphology in Cop1 regulated tumour development.