pubmed.ncbi.nlm.nih.gov

Oxidative stress inhibits the mitochondrial import of preproteins and leads to their degradation - PubMed

  • ️Mon Jan 01 2001

. 2001 Feb 1;263(1):107-17.

doi: 10.1006/excr.2000.5096.

Affiliations

Oxidative stress inhibits the mitochondrial import of preproteins and leads to their degradation

G Wright et al. Exp Cell Res. 2001.

Abstract

The mitochondrion depends upon the import of cytosolically synthesized preproteins for most of the proteins that comprise its structural elements and metabolic pathways. Here we have examined the influence of redox conditions on mitochondrial preprotein import and processing by mammalian mitochondria. Paraquat pretreatment of isolated mitochondria inhibited the subsequent import preornithine transcarbamylase (pOTC) in vitro. In intact cells oxidizing conditions led to decreased levels of mature OTC and accumulation of its preprotein. Implicating a mitochondrial import lesion, the fluorescence of pOTC-GFP (a protein in which the presequence of pOTC was fused to green fluorescent protein) transfected cells was decreased by paraquat treatment while cytosolic wild-type GFP remained largely unaffected. The accumulation of preproteins was enhanced by proteasome inhibitors. We observed that precursor proteins that failed to be imported, due to oxidizing conditions or an intrinsically slower import rate, are susceptible to degradation. Inhibition of the proteasome was also found to lead to higher levels of the translocase outer membrane protein 20 (Tom20) and to the perinuclear accumulation of mitochondria. These studies indicate that cellular redox conditions influence mitochondrial import, which, in turn, affects mitochondrial protein levels. A role for the proteasome in this process and in general mitochondrial function was also indicated.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources