Mitochondrial specialization revealed by single muscle fiber proteomics: Focus on the Krebs cycle

S. Schiaffino, C. Reggiani, Tatiana Kostrominova, M. Mann, M. Murgia

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We have developed a highly sensitive mass spectrometry-based proteomic workflow to examine the proteome of single muscle fibers. This study revealed significant differences in the mitochondrial proteome of the four major fiber types present in mouse skeletal muscle. Here, we focus on Krebs cycle enzymes and in particular on the differential distribution of the two mitochondrial isocitrate dehydrogenases, IDH2 and IDH3. Type 1/slow fibers contain high levels of IDH2 and relatively low levels of IDH3, whereas fast 2X and 2B fibers show an opposite expression pattern. The findings suggest that in skeletal muscle, IDH2 functions in the forward direction of the Krebs cycle and that substrate flux along the cycle occurs predominantly via IDH2 in type 1 fibers and via IDH3 in 2X and 2B fibers. IDH2-mediated conversion of isocitrate to α-ketoglutarate leads to the generation of NADPH, which is critical to buffering the H2O2 produced by the respiratory chain. Nicotinamide nucleotide transhydrogenase (NNT), the other major mito-chondrial enzyme involved in NADPH generation, is also more abundant in type 1 fibers. We suggest that the continuously active type 1 fibers are endowed with a more efficient H2O2 scavenging capacity to cope with the higher levels of reactive oxygen species production.

Original languageEnglish (US)
Pages (from-to)41-48
Number of pages8
JournalScandinavian Journal of Medicine and Science in Sports
Volume25
DOIs
StatePublished - Dec 1 2015

Fingerprint

Citric Acid Cycle
Proteome
NADP
Proteomics
Skeletal Muscle
NADP Transhydrogenases
Isocitrate Dehydrogenase
Muscles
Workflow
Enzymes
Reactive Oxygen Species
Mass Spectrometry
isocitric acid
Direction compound

Keywords

  • Isocitrate dehydrogenase
  • Metabolism
  • Muscle fibers
  • Reactive oxygen species
  • TCA cycle

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Mitochondrial specialization revealed by single muscle fiber proteomics : Focus on the Krebs cycle. / Schiaffino, S.; Reggiani, C.; Kostrominova, Tatiana; Mann, M.; Murgia, M.

In: Scandinavian Journal of Medicine and Science in Sports, Vol. 25, 01.12.2015, p. 41-48.

Research output: Contribution to journalArticle

@article{45b806098b9547e78495c1fe8677b983,
title = "Mitochondrial specialization revealed by single muscle fiber proteomics: Focus on the Krebs cycle",
abstract = "We have developed a highly sensitive mass spectrometry-based proteomic workflow to examine the proteome of single muscle fibers. This study revealed significant differences in the mitochondrial proteome of the four major fiber types present in mouse skeletal muscle. Here, we focus on Krebs cycle enzymes and in particular on the differential distribution of the two mitochondrial isocitrate dehydrogenases, IDH2 and IDH3. Type 1/slow fibers contain high levels of IDH2 and relatively low levels of IDH3, whereas fast 2X and 2B fibers show an opposite expression pattern. The findings suggest that in skeletal muscle, IDH2 functions in the forward direction of the Krebs cycle and that substrate flux along the cycle occurs predominantly via IDH2 in type 1 fibers and via IDH3 in 2X and 2B fibers. IDH2-mediated conversion of isocitrate to α-ketoglutarate leads to the generation of NADPH, which is critical to buffering the H2O2 produced by the respiratory chain. Nicotinamide nucleotide transhydrogenase (NNT), the other major mito-chondrial enzyme involved in NADPH generation, is also more abundant in type 1 fibers. We suggest that the continuously active type 1 fibers are endowed with a more efficient H2O2 scavenging capacity to cope with the higher levels of reactive oxygen species production.",
keywords = "Isocitrate dehydrogenase, Metabolism, Muscle fibers, Reactive oxygen species, TCA cycle",
author = "S. Schiaffino and C. Reggiani and Tatiana Kostrominova and M. Mann and M. Murgia",
year = "2015",
month = "12",
day = "1",
doi = "10.1111/sms.12606",
language = "English (US)",
volume = "25",
pages = "41--48",
journal = "Scandinavian Journal of Medicine and Science in Sports",
issn = "0905-7188",
publisher = "Blackwell Munksgaard",

}

TY - JOUR

T1 - Mitochondrial specialization revealed by single muscle fiber proteomics

T2 - Focus on the Krebs cycle

AU - Schiaffino, S.

AU - Reggiani, C.

AU - Kostrominova, Tatiana

AU - Mann, M.

AU - Murgia, M.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - We have developed a highly sensitive mass spectrometry-based proteomic workflow to examine the proteome of single muscle fibers. This study revealed significant differences in the mitochondrial proteome of the four major fiber types present in mouse skeletal muscle. Here, we focus on Krebs cycle enzymes and in particular on the differential distribution of the two mitochondrial isocitrate dehydrogenases, IDH2 and IDH3. Type 1/slow fibers contain high levels of IDH2 and relatively low levels of IDH3, whereas fast 2X and 2B fibers show an opposite expression pattern. The findings suggest that in skeletal muscle, IDH2 functions in the forward direction of the Krebs cycle and that substrate flux along the cycle occurs predominantly via IDH2 in type 1 fibers and via IDH3 in 2X and 2B fibers. IDH2-mediated conversion of isocitrate to α-ketoglutarate leads to the generation of NADPH, which is critical to buffering the H2O2 produced by the respiratory chain. Nicotinamide nucleotide transhydrogenase (NNT), the other major mito-chondrial enzyme involved in NADPH generation, is also more abundant in type 1 fibers. We suggest that the continuously active type 1 fibers are endowed with a more efficient H2O2 scavenging capacity to cope with the higher levels of reactive oxygen species production.

AB - We have developed a highly sensitive mass spectrometry-based proteomic workflow to examine the proteome of single muscle fibers. This study revealed significant differences in the mitochondrial proteome of the four major fiber types present in mouse skeletal muscle. Here, we focus on Krebs cycle enzymes and in particular on the differential distribution of the two mitochondrial isocitrate dehydrogenases, IDH2 and IDH3. Type 1/slow fibers contain high levels of IDH2 and relatively low levels of IDH3, whereas fast 2X and 2B fibers show an opposite expression pattern. The findings suggest that in skeletal muscle, IDH2 functions in the forward direction of the Krebs cycle and that substrate flux along the cycle occurs predominantly via IDH2 in type 1 fibers and via IDH3 in 2X and 2B fibers. IDH2-mediated conversion of isocitrate to α-ketoglutarate leads to the generation of NADPH, which is critical to buffering the H2O2 produced by the respiratory chain. Nicotinamide nucleotide transhydrogenase (NNT), the other major mito-chondrial enzyme involved in NADPH generation, is also more abundant in type 1 fibers. We suggest that the continuously active type 1 fibers are endowed with a more efficient H2O2 scavenging capacity to cope with the higher levels of reactive oxygen species production.

KW - Isocitrate dehydrogenase

KW - Metabolism

KW - Muscle fibers

KW - Reactive oxygen species

KW - TCA cycle

UR - http://www.scopus.com/inward/record.url?scp=84948431950&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84948431950&partnerID=8YFLogxK

U2 - 10.1111/sms.12606

DO - 10.1111/sms.12606

M3 - Article

C2 - 26589116

AN - SCOPUS:84948431950

VL - 25

SP - 41

EP - 48

JO - Scandinavian Journal of Medicine and Science in Sports

JF - Scandinavian Journal of Medicine and Science in Sports

SN - 0905-7188

ER -