Autophagy, P-Body Assembly, Mitochondrial Hyper-Fission, and Cell Death: Unexpected Secondary Roles of the Mediator Kinase Module Following Stress

Following unfavorable environmental cues, cells reprogram pathways that govern transcription, translation, and protein degradation systems. This reprogramming is essential to restore homeostasis or commit to cell death. This review focuses on the secondary roles of two nuclear transcriptional regulators, cyclin C and Med13, that play key roles in this decision processing. Both proteins are members of the Mediator kinase module (MKM) of the Mediator complex, which, under normal physiological conditions, positively and negatively regulates a subset of stress response genes. However, cyclin C and Med13 translocate to the cytoplasm following cell death and cell survival cue, respectively, interacting with a host of cell death and cell survival proteins. In the cytoplasm, cyclin C is required for stress-induced mitochondrial hyper-fission and promotes regulated cell death pathways. Cytoplasmic Med13 promotes stress-induced assembly of processing bodies (P-bodies) and is required for the autophagic degradation of a subset of P-body assembly factors by cargo hitchhiking autophagy. This review will focus on these secondary, a.k.a. "nigh" jobs" of "cyclin C and Med13, outlining the importance of these secondary functions in maintaining cellular homeostasis following stress.