Gene

Cell biology

Biology

Messenger RNA

Retrograde signaling

Signal transduction

Endoplasmic reticulum

Translation (biology)

Unfolded protein response

Genetics

Mitochondrial DNA

mitochondrial fusion

Integrated stress response

Mitochondrion

Transcription factor

ATF4

Cell Research

The mitochondrial network is not only required for the production of energy, essential cofactors and amino acids, but also serves as a signaling hub for innate immune and apoptotic pathways. Multiple mechanisms have evolved to identify and combat mitochondrial dysfunction to maintain the health of the organism. One such pathway is the mitochondrial unfolded protein response (UPRmt), which is regulated by the mitochondrial import efficiency of the transcription factor ATFS-1 in C. elegans and potentially orthologous transcription factors in mammals (ATF4, ATF5, CHOP). Upon mitochondrial dysfunction, import of ATFS-1 into mitochondria is reduced, allowing it to be trafficked to the nucleus where it promotes the expression of genes that promote survival and recovery of the mitochondrial network. Here, we discuss recent findings underlying UPRmt signal transduction and how this adaptive transcriptional response may interact with other mitochondrial stress response pathways.

UPRmt regulation and output: a stress response mediated by mitochondrial-nuclear communication