Mitochondrial unfolded protein response

The mitochondrial unfolded protein response (UPRmt) is a cellular stress response related to the mitochondria. The UPRmt results from unfolded or misfolded proteins in mitochondria beyond the capacity of chaperone proteins to handle them.[1] The UPRmt can occur either in the mitochondrial matrix or in the mitochondrial inner membrane.[1] In the UPRmt, the mitochondrion will either upregulate chaperone proteins or invoke proteases to degrade proteins that fail to fold properly.[1] UPRmt causes the sirtuin SIRT3 to activate antioxidant enzymes and mitophagy.[2]

Mitochondrial electron transport chain mutations that extend the life span of Caenorhabditis elegans (nematode worms) also activate the UPRmt.[3] Activation of the UPRmt in nematode worms by increasing NAD+ by supplementation with nicotinamide or nicotinamide riboside has been shown to extend lifespan.[4] Nicotinamide riboside supplementation in mice has also been shown to activate the UPRmt.[5]

See also

References

  1. 1 2 3 Pellegrino MW, Nargund AM, Haynes CM (2013). "Signaling the mitochondrial unfolded protein response". Biochimica et Biophysica Acta. 1833 (2): 410–416. doi:10.1016/j.bbamcr.2012.02.019. PMC 3393825. PMID 22445420.
  2. ↑ Papa L, Germain D (2014). "SirT3 regulates the mitochondrial unfolded protein response". Molecular and Cellular Biology. 34 (4): 699–710. doi:10.1128/MCB.01337-13. PMC 3911493. PMID 24324009.
  3. ↑ Durieux J, Wolff S, Dillin A (2011). "The cell-non-autonomous nature of electron transport chain-mediated longevity" (PDF). Cell. 144 (1): 79–91. doi:10.1016/j.cell.2010.12.016. PMC 3753670. PMID 21215371.
  4. ↑ Mouchiroud L, Houtkooper RH, Moullan N, Katsyuba E, Ryu D, Cantó C, Mottis A, Jo YS, Viswanathan M, Schoonjans K, Guarente L, Auwerx J (2013). "The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling" (PDF). Cell. 154 (2): 430–441. doi:10.1016/j.cell.2013.06.016. PMC 3062502. PMID 23870130.
  5. ↑ Zhang H, Ryu D, Wu Y, Gariani K, Wang X, Luan P, D'Amico D, Ropelle ER, Lutolf MP, Aebersold R, Schoonjans K, Menzies KJ, Auwerx J (2016). "NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice". Science. 352 (6292): 1436–1443. doi:10.1126/science.aaf2693. PMID 27127236.


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