MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo

Taylor A. Mattox, Martin E. Young, Carrie E. Rubel, Carolyn Spaniel, Jessica E. Rodríguez, Trisha J. Grevengoed, Mathias Gautel, Zhelong Xu, Ethan J. Anderson, Monte Willis

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

MuRF1 is a previously reported ubiquitin-ligase found in striated muscle that targets troponin I and myosin heavy chain for degradation. While MuRF1 has been reported to interact with mitochondrial substrates in yeast two-hybrid studies, no studies have identified MuRF1's role in regulating mitochondrial function to date. In the present study, we measured cardiac mitochondrial function from isolated permeabilized muscle fibers in previously phenotyped MuRF1 transgenic and MuRF1-/- mouse models to determine the role of MuRF1 in intermediate energy metabolism and ROS production. We identified a significant decrease in reactive oxygen species production in cardiac muscle fibers from MuRF1 transgenic mice with increased α-MHC driven MuRF1 expression. Increased MuRF1 expression in ex vivo and in vitro experiments revealed no alterations in the respiratory chain complex I and II function. Working perfusion experiments on MuRF1 transgenic hearts demonstrated significant changes in glucose oxidation. This is an factual error as written; however, total oxygen consumption was decreased. This data provides evidence for MuRF1 as a novel regulator of cardiac ROS, offering another mechanism by which increased MuRF1 expression may be cardioprotective in ischemia reperfusion injury, in addition to its inhibition of apoptosis via proteasome-mediate degradation of c-Jun. The lack of mitochondrial function phenotype identified in MuRF1-/- hearts may be due to the overlapping interactions of MuRF1 and MuRF2 with energy regulating proteins found by yeast two-hybrid studies reported here, implying a duplicity in MuRF1 and MuRF2's regulation of mitochondrial function.

Original languageEnglish (US)
Pages (from-to)173-187
Number of pages15
JournalJournal of Bioenergetics and Biomembranes
Volume46
Issue number3
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Transgenic Mice
Reactive Oxygen Species
Mitochondria
Electron Transport Complex I
Troponin I
Fungal Proteins
Striated Muscle
Myosin Heavy Chains
Proteasome Endopeptidase Complex
Ligases
Electron Transport
Ubiquitin
Reperfusion Injury
Oxygen Consumption
Energy Metabolism
Myocardium
Perfusion
Yeasts
Apoptosis
Phenotype

Keywords

  • Heart
  • Metabolism
  • Mitochondria
  • MuRF1
  • Ubiquitin ligase

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo. / Mattox, Taylor A.; Young, Martin E.; Rubel, Carrie E.; Spaniel, Carolyn; Rodríguez, Jessica E.; Grevengoed, Trisha J.; Gautel, Mathias; Xu, Zhelong; Anderson, Ethan J.; Willis, Monte.

In: Journal of Bioenergetics and Biomembranes, Vol. 46, No. 3, 01.01.2014, p. 173-187.

Research output: Contribution to journalArticle

Mattox, TA, Young, ME, Rubel, CE, Spaniel, C, Rodríguez, JE, Grevengoed, TJ, Gautel, M, Xu, Z, Anderson, EJ & Willis, M 2014, 'MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo', Journal of Bioenergetics and Biomembranes, vol. 46, no. 3, pp. 173-187. https://doi.org/10.1007/s10863-014-9549-9
Mattox, Taylor A. ; Young, Martin E. ; Rubel, Carrie E. ; Spaniel, Carolyn ; Rodríguez, Jessica E. ; Grevengoed, Trisha J. ; Gautel, Mathias ; Xu, Zhelong ; Anderson, Ethan J. ; Willis, Monte. / MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo. In: Journal of Bioenergetics and Biomembranes. 2014 ; Vol. 46, No. 3. pp. 173-187.
@article{215f8812d6184998bf04f938f79c91f7,
title = "MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo",
abstract = "MuRF1 is a previously reported ubiquitin-ligase found in striated muscle that targets troponin I and myosin heavy chain for degradation. While MuRF1 has been reported to interact with mitochondrial substrates in yeast two-hybrid studies, no studies have identified MuRF1's role in regulating mitochondrial function to date. In the present study, we measured cardiac mitochondrial function from isolated permeabilized muscle fibers in previously phenotyped MuRF1 transgenic and MuRF1-/- mouse models to determine the role of MuRF1 in intermediate energy metabolism and ROS production. We identified a significant decrease in reactive oxygen species production in cardiac muscle fibers from MuRF1 transgenic mice with increased α-MHC driven MuRF1 expression. Increased MuRF1 expression in ex vivo and in vitro experiments revealed no alterations in the respiratory chain complex I and II function. Working perfusion experiments on MuRF1 transgenic hearts demonstrated significant changes in glucose oxidation. This is an factual error as written; however, total oxygen consumption was decreased. This data provides evidence for MuRF1 as a novel regulator of cardiac ROS, offering another mechanism by which increased MuRF1 expression may be cardioprotective in ischemia reperfusion injury, in addition to its inhibition of apoptosis via proteasome-mediate degradation of c-Jun. The lack of mitochondrial function phenotype identified in MuRF1-/- hearts may be due to the overlapping interactions of MuRF1 and MuRF2 with energy regulating proteins found by yeast two-hybrid studies reported here, implying a duplicity in MuRF1 and MuRF2's regulation of mitochondrial function.",
keywords = "Heart, Metabolism, Mitochondria, MuRF1, Ubiquitin ligase",
author = "Mattox, {Taylor A.} and Young, {Martin E.} and Rubel, {Carrie E.} and Carolyn Spaniel and Rodr{\'i}guez, {Jessica E.} and Grevengoed, {Trisha J.} and Mathias Gautel and Zhelong Xu and Anderson, {Ethan J.} and Monte Willis",
year = "2014",
month = "1",
day = "1",
doi = "10.1007/s10863-014-9549-9",
language = "English (US)",
volume = "46",
pages = "173--187",
journal = "Journal of Bioenergetics and Biomembranes",
issn = "0145-479X",
publisher = "Springer New York",
number = "3",

}

TY - JOUR

T1 - MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo

AU - Mattox, Taylor A.

AU - Young, Martin E.

AU - Rubel, Carrie E.

AU - Spaniel, Carolyn

AU - Rodríguez, Jessica E.

AU - Grevengoed, Trisha J.

AU - Gautel, Mathias

AU - Xu, Zhelong

AU - Anderson, Ethan J.

AU - Willis, Monte

PY - 2014/1/1

Y1 - 2014/1/1

N2 - MuRF1 is a previously reported ubiquitin-ligase found in striated muscle that targets troponin I and myosin heavy chain for degradation. While MuRF1 has been reported to interact with mitochondrial substrates in yeast two-hybrid studies, no studies have identified MuRF1's role in regulating mitochondrial function to date. In the present study, we measured cardiac mitochondrial function from isolated permeabilized muscle fibers in previously phenotyped MuRF1 transgenic and MuRF1-/- mouse models to determine the role of MuRF1 in intermediate energy metabolism and ROS production. We identified a significant decrease in reactive oxygen species production in cardiac muscle fibers from MuRF1 transgenic mice with increased α-MHC driven MuRF1 expression. Increased MuRF1 expression in ex vivo and in vitro experiments revealed no alterations in the respiratory chain complex I and II function. Working perfusion experiments on MuRF1 transgenic hearts demonstrated significant changes in glucose oxidation. This is an factual error as written; however, total oxygen consumption was decreased. This data provides evidence for MuRF1 as a novel regulator of cardiac ROS, offering another mechanism by which increased MuRF1 expression may be cardioprotective in ischemia reperfusion injury, in addition to its inhibition of apoptosis via proteasome-mediate degradation of c-Jun. The lack of mitochondrial function phenotype identified in MuRF1-/- hearts may be due to the overlapping interactions of MuRF1 and MuRF2 with energy regulating proteins found by yeast two-hybrid studies reported here, implying a duplicity in MuRF1 and MuRF2's regulation of mitochondrial function.

AB - MuRF1 is a previously reported ubiquitin-ligase found in striated muscle that targets troponin I and myosin heavy chain for degradation. While MuRF1 has been reported to interact with mitochondrial substrates in yeast two-hybrid studies, no studies have identified MuRF1's role in regulating mitochondrial function to date. In the present study, we measured cardiac mitochondrial function from isolated permeabilized muscle fibers in previously phenotyped MuRF1 transgenic and MuRF1-/- mouse models to determine the role of MuRF1 in intermediate energy metabolism and ROS production. We identified a significant decrease in reactive oxygen species production in cardiac muscle fibers from MuRF1 transgenic mice with increased α-MHC driven MuRF1 expression. Increased MuRF1 expression in ex vivo and in vitro experiments revealed no alterations in the respiratory chain complex I and II function. Working perfusion experiments on MuRF1 transgenic hearts demonstrated significant changes in glucose oxidation. This is an factual error as written; however, total oxygen consumption was decreased. This data provides evidence for MuRF1 as a novel regulator of cardiac ROS, offering another mechanism by which increased MuRF1 expression may be cardioprotective in ischemia reperfusion injury, in addition to its inhibition of apoptosis via proteasome-mediate degradation of c-Jun. The lack of mitochondrial function phenotype identified in MuRF1-/- hearts may be due to the overlapping interactions of MuRF1 and MuRF2 with energy regulating proteins found by yeast two-hybrid studies reported here, implying a duplicity in MuRF1 and MuRF2's regulation of mitochondrial function.

KW - Heart

KW - Metabolism

KW - Mitochondria

KW - MuRF1

KW - Ubiquitin ligase

UR - http://www.scopus.com/inward/record.url?scp=84903552840&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903552840&partnerID=8YFLogxK

U2 - 10.1007/s10863-014-9549-9

DO - 10.1007/s10863-014-9549-9

M3 - Article

VL - 46

SP - 173

EP - 187

JO - Journal of Bioenergetics and Biomembranes

JF - Journal of Bioenergetics and Biomembranes

SN - 0145-479X

IS - 3

ER -