Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Jun;1863(6 Pt A):1298-306.
doi: 10.1016/j.bbamcr.2016.03.023. Epub 2016 Mar 28.

Oxidative folding in the mitochondrial intermembrane space: A regulated process important for cell physiology and disease

Afroditi Chatzi  1 , Phanee Manganas  1 , Kostas Tokatlidis  2
Affiliations
Review

Oxidative folding in the mitochondrial intermembrane space: A regulated process important for cell physiology and disease

Afroditi Chatzi et al. Biochim Biophys Acta. 2016 Jun.

Abstract

Mitochondria are fundamental organelles with a complex internal architecture that fulfill important diverse functions including iron-sulfur cluster assembly and cell respiration. Intense work for more than 30 years has identified the key protein import components and the pathways involved in protein targeting and assembly. More recently, oxidative folding has been discovered as one important mechanism for mitochondrial proteostasis whilst several human disorders have been linked to this pathway. We describe the molecular components of this pathway in view of their putative redox regulation and we summarize available evidence on the connections of these pathways to human disorders.

Keywords: Erv1; Mia40; Mitochondrial intermembrane space; Mitochondrial protein import; Oxidative protein folding; Thiol-disulfide exchange.

PubMed Disclaimer

Figures

Image 1
Graphical abstract
Fig. 1:
Fig. 1
Mitochondrial import pathways. Cytosolic chaperones (Hsp70/90) are responsible for targeting of the precursors to the mitochondrial outer membrane. After interacting with the TOM complex, the preproteins enter the IMS following different sorting pathways (depicted with the different colors) to reach their final destination within the organelle.
Fig. 2:
Fig. 2
The Mia40 population in the IMS. Mia40 in the IMS functions as an import receptor, a chaperone and as the key oxidoreductase that introduces disulfide bonds to the incoming precursors. In this process, the electrons from the precursor flow to Mia40 then to Erv1 and finally to Cytochrome C. This pathway engages Mia40-redox active population. It has been suggested that a part of the total Mia40 population binds iron/sulfur clusters in a dimer form (Fe/S-bound population). This Mia40 population is considered redox inactive and its function is yet unknown.
Fig. 3:
Fig. 3
Molecular machineries underpinning redox regulation. The synthesis of glutathione occurs in both the cytosol and the mitochondrial matrix, where there is also a complete Trx system. Other redox regulating protein factors that can be found associated or within mitochondria are Gpx proteins, Grx2, the catalase Cta1 and the SOD proteins. Although functional parallels can be drawn between the cytosolic and mitochondrial systems, the exact nature of the dual localization of some common components and the links to the oxidative folding system remain unknown.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Horvath S.E., Daum G. Lipids of mitochondria. Prog. Lipid Res. 2013:590–614. - PubMed
    1. Tamura Y., Sesaki H., Endo T. Phospholipid transport via mitochondria. Traffic. 2014;15:933–945. - PMC - PubMed
    1. Baile M.G., Lu Y.-W., Claypool S.M. The topology and regulation of cardiolipin biosynthesis and remodeling in yeast. Chem. Phys. Lipids. 2014;179:25–31. - PMC - PubMed
    1. Joza N., Susin S.A., Daugas E., Stanford W.L., Cho S.K., Li C.Y., Sasaki T., Elia A.J., Cheng H.Y., Ravagnan L., Ferri K.F., Zamzami N., Wakeham A., Hakem R., Yoshida H., Kong Y.Y., Mak T.W., Zúñiga-Pflücker J.C., Kroemer G., Penninger J.M. Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature. 2001;410:549–554. - PubMed
    1. Lill R. Function and biogenesis of iron–sulphur proteins. Nature. 2009;460:831–838. - PubMed

Publication types

MeSH terms

Substances