Stomatin-like protein 2 deficiency results in impaired mitochondrial translation

© 2017 Mitsopoulos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Mitochondria translate the RNAs for 13...

Full description

Saved in:
Bibliographic Details
Main Authors: Mitsopoulos P., Lapohos O., Weraarpachai W., Antonicka H., Chang Y., Madrenas J.
Format: Journal
Published: 2017
Online Access:https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85021382772&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/40417
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Chiang Mai University
id th-cmuir.6653943832-40417
record_format dspace
spelling th-cmuir.6653943832-404172017-09-28T04:09:28Z Stomatin-like protein 2 deficiency results in impaired mitochondrial translation Mitsopoulos P. Lapohos O. Weraarpachai W. Antonicka H. Chang Y. Madrenas J. © 2017 Mitsopoulos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Mitochondria translate the RNAs for 13 core polypeptides of respiratory chain and ATP synthase complexes that are essential for the assembly and function of these complexes. This process occurs in close proximity to the mitochondrial inner membrane. However, the mechanisms and molecular machinery involved in mitochondrial translation are not fully understood, and defects in this process can result in severe diseases. Stomatin-like protein (SLP)-2 is a mainly mitochondrial protein that forms cardiolipin- and prohibitin-enriched microdomains in the mitochondrial inner membrane that are important for the formation of respiratory supercomplexes and their function. Given this regulatory role of SLP-2 in processes closely associated with the mitochondrial inner membrane, we hypothesized that the function of SLP-2 would have an impact on mitochondrial translation. 35 S-Methionine/cysteine pulse labeling of resting or activated T cells from T cell-specific Slp-2 knockout mice showed a significant impairment in the production of several mitochondrial DNA-encoded polypeptides following T cell activation, including Cytb, COXI, COXII, COXIII, and ATP6. Measurement of mitochondrial DNA stability and mitochondrial transcription revealed that this impairment was at the post-transcriptional level. Examination of mitochondrial ribosome assembly showed that SLP-2 migrated in sucrose-density gradients similarly to the large ribosomal subunit but that its deletion at the genetic level did not affect mitochondrial ribosome assembly. Functionally, the impairment in mitochondrial translation correlated with decreased interleukin-2 production in activated T cells. Altogether, these data show that SLP-2 acts as a general regulator of mitochondrial translation. 2017-09-28T04:09:28Z 2017-09-28T04:09:28Z 6 Journal 2-s2.0-85021382772 10.1371/journal.pone.0179967 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85021382772&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/40417
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
description © 2017 Mitsopoulos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Mitochondria translate the RNAs for 13 core polypeptides of respiratory chain and ATP synthase complexes that are essential for the assembly and function of these complexes. This process occurs in close proximity to the mitochondrial inner membrane. However, the mechanisms and molecular machinery involved in mitochondrial translation are not fully understood, and defects in this process can result in severe diseases. Stomatin-like protein (SLP)-2 is a mainly mitochondrial protein that forms cardiolipin- and prohibitin-enriched microdomains in the mitochondrial inner membrane that are important for the formation of respiratory supercomplexes and their function. Given this regulatory role of SLP-2 in processes closely associated with the mitochondrial inner membrane, we hypothesized that the function of SLP-2 would have an impact on mitochondrial translation. 35 S-Methionine/cysteine pulse labeling of resting or activated T cells from T cell-specific Slp-2 knockout mice showed a significant impairment in the production of several mitochondrial DNA-encoded polypeptides following T cell activation, including Cytb, COXI, COXII, COXIII, and ATP6. Measurement of mitochondrial DNA stability and mitochondrial transcription revealed that this impairment was at the post-transcriptional level. Examination of mitochondrial ribosome assembly showed that SLP-2 migrated in sucrose-density gradients similarly to the large ribosomal subunit but that its deletion at the genetic level did not affect mitochondrial ribosome assembly. Functionally, the impairment in mitochondrial translation correlated with decreased interleukin-2 production in activated T cells. Altogether, these data show that SLP-2 acts as a general regulator of mitochondrial translation.
format Journal
author Mitsopoulos P.
Lapohos O.
Weraarpachai W.
Antonicka H.
Chang Y.
Madrenas J.
spellingShingle Mitsopoulos P.
Lapohos O.
Weraarpachai W.
Antonicka H.
Chang Y.
Madrenas J.
Stomatin-like protein 2 deficiency results in impaired mitochondrial translation
author_facet Mitsopoulos P.
Lapohos O.
Weraarpachai W.
Antonicka H.
Chang Y.
Madrenas J.
author_sort Mitsopoulos P.
title Stomatin-like protein 2 deficiency results in impaired mitochondrial translation
title_short Stomatin-like protein 2 deficiency results in impaired mitochondrial translation
title_full Stomatin-like protein 2 deficiency results in impaired mitochondrial translation
title_fullStr Stomatin-like protein 2 deficiency results in impaired mitochondrial translation
title_full_unstemmed Stomatin-like protein 2 deficiency results in impaired mitochondrial translation
title_sort stomatin-like protein 2 deficiency results in impaired mitochondrial translation
publishDate 2017
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85021382772&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/40417
_version_ 1681421806042349568