UXT (Ubiquitously Expressed Transcript) causes mitochondrial aggregation

Abstract

Mitochondria are the bioenergetic and metabolic centers in eukaryotic cells and play a central role in apoptosis. Mitochondrial distribution is controlled by the microtubular cytoskeleton. The perinuclear aggregation of mitochondria is one of the characteristics associated with some types of cell death. Control of mitochondrial aggregation particularly related to cell death events is poorly understood. Previously, we identified ubiquitously expressed transcript (UXT) as a potential component of mitochondrial associated LRPPRC, a multidomain organizer that potentially integrates mitochondria and the microtubular cytoskeleton with chromosome remodeling. Here we show that when overexpressed in mammalian cells, green fluorescent protein-tagged UXT (GFP-UXT) exhibits four types of distribution patterns that are proportional to the protein level, and increase with time. UXT initially was dispersed in the extranuclear cytosol, then appeared in punctate cytosolic dots, then an intense perinuclear aggregation that eventually invaded and disrupted the nucleus. The punctate cytosolic aggregates of GFP-UXT coincided with aggregates of mitochondria and LRPPRC. We conclude that increasing concentrations of UXT contributes to progressive aggregation of mitochondria and cell death potentially through association of UXT with LRPPRC.