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

Fernando Gomes; Helena Turano; Angélica Ramos; Mário Henrique de Barros; Luciana A Haddad; Luis E S Netto

doi:10.1007/s12551-021-00899-2

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

Biophys Rev. 2021 Nov 10;13(6):983-994. doi: 10.1007/s12551-021-00899-2. eCollection 2021 Dec.

Authors

Fernando Gomes¹, Helena Turano¹, Angélica Ramos¹, Mário Henrique de Barros², Luciana A Haddad¹, Luis E S Netto¹

Affiliations

¹ Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, 05508-090 Brazil.
² Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, 05508-900 Brazil.

Abstract

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

Keywords: H2O2; Intermembrane space; Matrix; Mitochondria; Peroxiredoxin; Presequence.

Publication types

Review