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.…

• EC
  European Commission

  Award: 803565
• DF
  Deutsche Forschungsgemeinschaft

  Awards: 403765277, SFB1531, 390339347, SFB1177, 259130777, 456687919
• UZ
  Universität zu Köln