- Open Access
Proteasomal degradation competes with Mia40-mediated import into mitochondria
© Herrmann et al. 2018
- Published: 22 June 2018
The original article was published in BMC Biology 2018 16:66
Tandem fluorescent protein timers are elegant tools to determine proteolytic stabilities of cytosolic proteins with high spatial and temporal resolution. In a new study published in BMC Biology, Kowalski et al. fused timers to precursors of proteins of the mitochondrial intermembrane space and found that they are under surveillance of the ubiquitin-proteasome system. Ubiquitination at lysine residues of these precursors directly inhibits their translocation into the intermembrane space and targets them for proteasomal degradation.
We thank the Deutsche Forschungsgemeinschaft (IRTG 1830 and DIP MitoBalance) for financial support.
All authors contributed in writing the article and designed the figure. All authors have read and agreed the content.
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Morgenstern M, Stiller SB, Lubbert P, Peikert CD, Dannenmaier S, Drepper F, Weill U, Hoss P, Feuerstein R, Gebert M, et al. Definition of a high-confidence mitochondrial proteome at quantitative scale. Cell Rep. 2017;19(13):2836–52.View ArticlePubMedPubMed CentralGoogle Scholar
- Peleh V, Cordat E, Herrmann JM. Mia40 is a trans-site receptor that drives protein import into the mitochondrial intermembrane space by hydrophobic substrate binding. elife. 2016;5:e16177.View ArticlePubMedPubMed CentralGoogle Scholar
- Fischer M, Horn S, Belkacemi A, Kojer K, Petrungaro C, Habich M, Ali M, Kuttner V, Bien M, Kauff F, et al. Protein import and oxidative folding in the mitochondrial intermembrane space of intact mammalian cells. Mol Biol Cell. 2013;24(14):2160–70.View ArticlePubMedPubMed CentralGoogle Scholar
- Kowalski L, Bragoszewski P, Khmelinskii A, Glow E, Knop M, Chacinska A. Determinants of the cytosolic turnover of mitochondrial intermembrane space proteins. BMC Biol in press. https://doi.org/10.1186/s12915-018-0536-1.
- Khmelinskii A, Meurer M, Ho CT, Besenbeck B, Fuller J, Lemberg MK, Bukau B, Mogk A, Knop M. Incomplete proteasomal degradation of green fluorescent proteins in the context of tandem fluorescent protein timers. Mol Biol Cell 2016;27(2):360–0.Google Scholar
- Bragoszewski P, Gornicka A, Sztolsztener ME, Chacinska A. The ubiquitin-proteasome system regulates mitochondrial intermembrane space proteins. Mol Cell Biol. 2013;33(11):2136–48.View ArticlePubMedPubMed CentralGoogle Scholar
- Pearce DA, Sherman F. Differential ubiquitin-dependent degradation of the yeast apo-cytochrome c isozymes. J Biol Chem. 1997;272(50):31829–36.View ArticlePubMedGoogle Scholar
- Belgareh-Touze N, Cavellini L, Cohen MM. Ubiquitination of ERMES components by the E3 ligase Rsp5 is involved in mitophagy. Autophagy. 2017;13(1):114–32.View ArticlePubMedGoogle Scholar
- Weidberg H, Amon A. MitoCPR-A surveillance pathway that protects mitochondria in response to protein import stress. Science. 2018;360(6385):eaan4146.View ArticlePubMedGoogle Scholar
- Wrobel L, Topf U, Bragoszewski P, Wiese S, Sztolsztener ME, Oeljeklaus S, Varabyova A, Lirski M, Chroscicki P, Mroczek S, et al. Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol. Nature. 2015;524(7566):485–8.View ArticlePubMedGoogle Scholar