CROSSTALK BETWEEN UBIQUITINATION AND ADP-RIBOSYLATION IN THE MAINTENANCE OF MITOCHONDRIAL HOMEOSTASIS

Oxidative stress and increased ROS production, as observed in aging and obesity, commonly lead to the accumulation of mitochondrial dysfunctions. This is met by the activation of a robust mitochondria-to-nucleus stress response promoting the rewiring of nuclear gene expression to limit cellular and tissue damage and promote organelle adaptation. Here we will review previous work uncovering the transcriptional cofactor G-Protein Pathway Suppressor 2 (GPS2) as a mediator of mitochondria retrograde signaling and a key nuclear regulator of nuclear-encoded mitochondrial genes, including mitochondrial chaperones/proteases, mitokines, and other protective enzymes such as the ADP-ribosyltransferase NEURL4. We will also discuss unpublished work showing that shuttling of GPS2 between organelles plays a role in coordinating the transcriptional and translational regulation of antioxidant factors and pro-apoptotic genes by promoting the ubiquitination of mitochondria-associated translation factors.