Crossref journal-article
Portland Press Ltd.
Biochemical Journal (288)
Abstract

When incubated with mitochondria in an air atmosphere, menadione and doxorubicin (which redox cycle with the respiratory chain to produce oxygen radicals), as well as xanthine oxidase plus xanthine (which generate superoxide and H2O2), stimulated the degradation of newly-synthesized [(3H]leucine-labelled) mitochondrial polypeptides. No stimulation was observed in an N2 atmosphere, ATP was not required, and xanthine oxidase was not effective without xanthine. Various forms of oxidative stress induced varying degrees of protein cross-linking, protein fragmentation and proteolysis, as judged by gel electrophoresis and amino acid analysis. To learn more about the proteolytic enzymes involved in degradation, we undertook studies with purified protein substrates which had been exposed to oxidative stress (OH or H2O2) in vitro. Despite mitochondrial contamination with acid proteases of lysosomal (and other) origin, pH profiles revealed distinct proteolytic activities at both pH 4 and pH 8. The pH 8 activity preferentially degraded the oxidatively-denatured forms of haemoglobin, albumin and superoxide dismutase; was unaffected by digitonin; and exhibited a several-fold increase in activity upon mitochondrial disruption (highest activity being found in the matrix). In contrast, the pH 4 activity was dramatically decreased by digitonin treatment (to reduce lysosomal contamination); was unaffected by mitochondrial disruption; and showed no preference for oxidatively-denatured proteins. The pH 8 activity was not stimulated by ATP, but was inhibited by EDTA, haemin and phenylmethylsulphonyl fluoride. In contrast, the contaminating pH 4 activity was only inhibited by pepstatin and leupeptin. Thus, our experiments reveal a distinct mitochondrial (matrix) proteolytic pathway which can preferentially degrade oxidatively-denatured proteins.

Bibliography

Marcillat, O., Zhang, Y., Lin, S. W., & Davies, K. J. (1988). Mitochondria contain a proteolytic system which can recognize and degrade oxidatively-denatured proteins. Biochemical Journal, 254(3), 677–683.

Authors 4
  1. O Marcillat (first)
  2. Y Zhang (additional)
  3. S W Lin (additional)
  4. K J Davies (additional)
References 0 Referenced 103

None

Dates
Type When
Created 10 years ago (Aug. 10, 2015, 5:11 p.m.)
Deposited 3 years, 9 months ago (Nov. 25, 2021, 1:29 p.m.)
Indexed 1 month ago (July 25, 2025, 6:56 a.m.)
Issued 36 years, 11 months ago (Sept. 15, 1988)
Published 36 years, 11 months ago (Sept. 15, 1988)
Published Print 36 years, 11 months ago (Sept. 15, 1988)
Funders 0

None

@article{Marcillat_1988, title={Mitochondria contain a proteolytic system which can recognize and degrade oxidatively-denatured proteins}, volume={254}, ISSN={1470-8728}, url={http://dx.doi.org/10.1042/bj2540677}, DOI={10.1042/bj2540677}, number={3}, journal={Biochemical Journal}, publisher={Portland Press Ltd.}, author={Marcillat, O and Zhang, Y and Lin, S W and Davies, K J}, year={1988}, month=sep, pages={677–683} }