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Mitochondrial translocation of APE1 relies on the MIA pathway. | LitMetric

Mitochondrial translocation of APE1 relies on the MIA pathway.

Nucleic Acids Res

Department of Medical and Biological Sciences, University of Udine, Udine 33100, Italy

Published: June 2015

AI Article Synopsis

  • - APE1 is a crucial protein that helps repair DNA in both nuclei and mitochondria, but its movement within cells is not fully understood yet, especially how it gets into mitochondria.
  • - Research shows that APE1 interacts with a protein called Mia40, which assists in transporting it into mitochondria through a process that relies on disulfide bond formation and a redox system.
  • - The study concludes that Mia40 levels influence APE1's entry into mitochondria, which is important for keeping mitochondrial DNA stable and supporting cell survival.

Article Abstract

APE1 is a multifunctional protein with a fundamental role in repairing nuclear and mitochondrial DNA lesions caused by oxidative and alkylating agents. Unfortunately, comprehensions of the mechanisms regulating APE1 intracellular trafficking are still fragmentary and contrasting. Recent data demonstrate that APE1 interacts with the mitochondrial import and assembly protein Mia40 suggesting the involvement of a redox-assisted mechanism, dependent on the disulfide transfer system, to be responsible of APE1 trafficking into the mitochondria. The MIA pathway is an import machinery that uses a redox system for cysteine enriched proteins to drive them in this compartment. It is composed by two main proteins: Mia40 is the oxidoreductase that catalyzes the formation of the disulfide bonds in the substrate, while ALR reoxidizes Mia40 after the import. In this study, we demonstrated that: (i) APE1 and Mia40 interact through disulfide bond formation; and (ii) Mia40 expression levels directly affect APE1's mitochondrial translocation and, consequently, play a role in the maintenance of mitochondrial DNA integrity. In summary, our data strongly support the hypothesis of a redox-assisted mechanism, dependent on Mia40, in controlling APE1 translocation into the mitochondrial inner membrane space and thus highlight the role of this protein transport pathway in the maintenance of mitochondrial DNA stability and cell survival.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477663PMC
http://dx.doi.org/10.1093/nar/gkv433DOI Listing

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