Single cell analysis of a iPSC-derived glial-neurons triculture model of mitochondrial unfolded protein response (UPRmt) activation.

Research in simpler organisms has demonstrated that UPRmt activation in glial cells promotes protein homeostasis through beneficial cell-nonautonomous communication to neurons. To address the role of mitochondrial stress responses in the human brain we profiled the cell-type-specific role of human UPRmt using human induced pluripotent stem cell (iPSC)-derived neuronal and glial tricultures.

We found that UPRmt activation disrupted intercellular communication among neuronal and glial cells, leading to microglial phagocytic pathways dysfunction and increased inflammatory signaling.