Dissecting the molecular mechanisms of mitochondrial import and maturation of peroxiredoxins from yeast and mammalian cells

Peroxiredoxins (Prxs) are cysteine-based peroxidases that play a central role in keeping the H 2 O 2 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 a...

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Bibliographic Details
Published in:Biophysical reviews 2021-12, Vol.13 (6), p.983-994
Main Authors: Gomes, Fernando, Turano, Helena, Ramos, Angélica, de Barros, Mário Henrique, Haddad, Luciana A., Netto, Luis E. S.
Format: Article
Language:English
Subjects:
Biochemistry
Biological and Medical Physics
Biological Techniques
Biomedical and Life Sciences
Biophysics
Cell Biology
Cytosol
Hydrogen peroxide
Imports
Isoforms
Life Sciences
Mammalian cells
Mammals
Maturation
Membrane Biology
Mitochondria
Molecular modelling
Nanotechnology
Proteins
Review
State-of-the-art reviews
Substrates
Yeast
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Summary:Peroxiredoxins (Prxs) are cysteine-based peroxidases that play a central role in keeping the H 2 O 2 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 H 2 O 2 , understanding the mitochondrial Prx biogenesis pathways is essential to increase our knowledge about the H 2 O 2 -dependent cellular signaling, which is relevant to the pathophysiology of some human diseases.
ISSN:1867-2450
1867-2469
DOI:10.1007/s12551-021-00899-2