A cytosolic surveillance mechanism activates the mitochondrial UPR.

ABSTRACT: The mitochondrial unfolded protein response (UPR^mt) is essential to safeguard mitochondria from proteotoxic damage by activating a dedicated transcriptional response in the nucleus to restore proteostasis^1,2. Yet, it remains unclear how the information on mitochondria misfolding stress (MMS) is signalled to the nucleus as part of the human UPR^mt (refs. ^3,4). Here, we show that UPR^mt signalling is driven by the release of two individual signals in the cytosol-mitochondrial reactive oxygen species (mtROS) and accumulation of mitochondrial protein precursors in the cytosol (c-mtProt). Combining proteomics and genetic approaches, we identified that MMS causes the release of mtROS into the cytosol. In parallel, MMS leads to mitochondrial pr

SUBMITTER: Sutandy FXR 

PROVIDER: S-EPMC10284689 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature