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Intermediate filaments (IFs) provide crucial structural support in higher eukaryotic cells.Accumulating evidences demonstrate that intermediate filaments also participate in various cellular activities including stress responses,cell growth,cell death and cell migration through dynamic interactions with various non-structure proteins.Here we report the identification of Pirh2,a RING-H2-type ubiquitin E3 ligase,as a novel binding partner of the cytoplasmic intermediate filament proteins Keratin 8/18 (K8/18).Phosphorylation of either Pirh2 or K8/18 affects their association.Although Pirh2 was not found to influence the stability of K8/18,it displayed an unexpected role in regulating the organization of the network of K8/18 keratin filaments.UV irradiation or knockdown with either Pirh2 or K18 led to mitochondrial redistribution,and this process is likely through a microtubule-mediated pathway.The abnormal localization of mitochondria in Pirh2-knockdown cells may partially accounts for its increased cell sensitivity to UV-induced apoptosis,probably through enhancing the release of proapoptotic proteins,such as cytochrome c and Smac/DIABLO to the cytosol.Overall,our data reveals a novel role of the Pirh2-K8/18 complex in governing the distribution of mitochondria.