Year: 2025
Type: article
Abstract: Mitochondria are central hubs of cellular metabolism and their dysfunction has been implicated in a variety of human pathologies and the onset of aging. To ensure proper mitochondrial function under misfolding stress, a retrograde mitochondrial signaling pathway known as UPR mt is activated. The UPR mt ensures that mitochondrial stress is communicated to the nucleus, where gene expression for several mitochondrial proteases and chaperones is induced, forming a protective mechanism to restore mitochondrial proteostasis and function. Importantly, the UPR mt not only acts within cells, but also exhibits a conserved cell-nonautonomous activation across species, where mitochondrial stress in a defined tissue triggers a systemic response that affects distant organs. Here, we summarize the molecular basis of the UPR mt in the invertebrate model organism Caenorhabditis elegans and in mammals. We also describe recent findings on cell-nonautonomous activation of the UPR mt in worms, flies and mice, and how UPR mt activation in specific tissues affects organismal metabolism and longevity.
Source: Biological Chemistry
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid:
Funder: Deutsche Forschungsgemeinschaft
OpenAlex ID: W4409482227