Abstract
Peroxiredoxins (Prxs) are cysteine-based peroxidases that play a central role in kee** the H2O2 at physiological levels. Eukaryotic cells express different Prxs isoforms, which differ in their subcellular locations and substrate specificities. Mitochondrial Prxs are synthesized in the cytosol as precursor proteins containing N-terminal cleavable presequences that act as mitochondrial targeting signals. Due to the fact that presequence controls the import of the vast majority of mitochondrial matrix proteins, the mitochondrial Prxs were initially predicted to be localized exclusively in the matrix. However, recent studies showed that mitochondrial Prxs are also targeted to the intermembrane space by mechanisms that remain poorly understood. While in yeast the IMP complex can translocate Prx1 to the intermembrane space, the maturation of yeast Prx1 and mammalian Prdx3 and Prdx5 in the matrix has been associated with sequential cleavages of the presequence by MPP and Oct1/MIP proteases. In this review, we describe the state of the art of the molecular mechanisms that control the mitochondrial import and maturation of Prxs of yeast and human cells. Once mitochondria are considered the major intracellular source of H2O2, understanding the mitochondrial Prx biogenesis pathways is essential to increase our knowledge about the H2O2-dependent cellular signaling, which is relevant to the pathophysiology of some human diseases.
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Our work was supported by research grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grants 2013/07937–8 and 2013/08028–1. Fernando Gomes and Helena Turano are also supported by FAPESP, grants 2017/09443–3 and 2017/23839–7, respectively. Angélica Ramos is also supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
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Gomes, F., Turano, H., Ramos, A. et al. Dissecting the molecular mechanisms of mitochondrial import and maturation of peroxiredoxins from yeast and mammalian cells. Biophys Rev 13, 983–994 (2021). https://doi.org/10.1007/s12551-021-00899-2
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DOI: https://doi.org/10.1007/s12551-021-00899-2