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

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, T Y

AU - Mann, M

AU - Murgia, M

N1 - © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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 H2 O2 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 H2 O2 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 H2 O2 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 H2 O2 scavenging capacity to cope with the higher levels of reactive oxygen species production.

U2 - 10.1111/sms.12606

DO - 10.1111/sms.12606

M3 - Review

C2 - 26589116

SN - 0905-7188

VL - 25

SP - 41

EP - 48

JO - Scandinavian Journal of Medicine & Science in Sports

JF - Scandinavian Journal of Medicine & Science in Sports

IS - Suppl 4

ER -