Maturation of mitochondrially targeted prx v involves a second cleavage by mitochondrial intermediate peptidase that is sensitive to inhibition by h2o2

Juhyun Sim, Jiyoung Park, Hyun Ae Woo, Sue Goo Rhee

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Prx V mRNA contains two in-frame AUG codons, producing a long (L-Prx V) and short form of Prx V (S-Prx V), and mouse L-Prx V is expressed as a precursor protein containing a 49-amino acid N-terminal mitochondria targeting sequence. Here, we show that the N-terminal 41-residue sequence of L-Prx V is cleaved by mitochondrial processing peptidase (MPP) in the mitochondrial matrix to produce an intermediate Prx V (I-Prx V) with a destabilizing phenylalanine at its N-terminus, and further, that the next 8-residue sequence is cleaved by mitochondrial intermediate peptidase (MIP) to convert I-Prx V to a stabilized mature form that is identical to S-Prx V. Further, we show that when mitochondrial H2O2 levels are increased in HeLa cells using rotenone, in several mouse tissues by deleting Prx III, and in the adrenal gland by deleting Srx or by exposing mice to immobilized stress, I-Prx V accumulates transiently and mature S-Prx V levels decrease in mitochondria over time. These findings support the view that MIP is inhibited by H2O2, resulting in the accumulation and subsequent degradation of I-Prx V, identifying a role for redox mediated regulation of Prx V proteolytic maturation and expression in mitochondria.

Original languageEnglish
Article number346
Pages (from-to)1-15
Number of pages15
JournalAntioxidants
Volume10
Issue number3
DOIs
StatePublished - Mar 2021

Keywords

  • Hydrogen peroxide
  • Mitochondria targeting sequence
  • Mitochondrial intermediate pepti-dase
  • Peroxiredoxin V

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