Single muscle fiber proteomics reveals unexpected mitochondrial specialization

TY - JOUR

T1 - Single muscle fiber proteomics reveals unexpected mitochondrial specialization

AU - Murgia, Marta

AU - Nagaraj, Nagarjuna

AU - Deshmukh, Atul S

AU - Zeiler, Marlis

AU - Cancellara, Pasqua

AU - Moretti, Irene

AU - Reggiani, Carlo

AU - Schiaffino, Stefano

AU - Mann, Matthias

N1 - © 2015 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Mammalian skeletal muscles are composed of multinucleated cells termed slow or fast fibers according to their contractile and metabolic properties. Here, we developed a high-sensitivity workflow to characterize the proteome of single fibers. Analysis of segments of the same fiber by traditional and unbiased proteomics methods yielded the same subtype assignment. We discovered novel subtype-specific features, most prominently mitochondrial specialization of fiber types in substrate utilization. The fiber type-resolved proteomes can be applied to a variety of physiological and pathological conditions and illustrate the utility of single cell type analysis for dissecting proteomic heterogeneity. Synopsis Here, single multinucleated muscle fibers are analyzed by high sensitivity proteomics for the first time. This reveals an unexpected diversity and specialization in metabolic properties of individual fiber types, in particular in mitochondrial function. First single skeletal muscle fiber proteome, and thereby single cell proteome of any kind Single-shot proteomic analysis captures main features of type 1-slow and of the subtypes of fast fibers Qualitative differences in the mitochondrial proteome of the four fiber types uncover a metabolic specialization Here, single multinucleated muscle fibers are analyzed by high sensitivity proteomics for the first time. This reveals an unexpected diversity and specialization in metabolic properties of individual fiber types, in particular in mitochondrial function.

AB - Mammalian skeletal muscles are composed of multinucleated cells termed slow or fast fibers according to their contractile and metabolic properties. Here, we developed a high-sensitivity workflow to characterize the proteome of single fibers. Analysis of segments of the same fiber by traditional and unbiased proteomics methods yielded the same subtype assignment. We discovered novel subtype-specific features, most prominently mitochondrial specialization of fiber types in substrate utilization. The fiber type-resolved proteomes can be applied to a variety of physiological and pathological conditions and illustrate the utility of single cell type analysis for dissecting proteomic heterogeneity. Synopsis Here, single multinucleated muscle fibers are analyzed by high sensitivity proteomics for the first time. This reveals an unexpected diversity and specialization in metabolic properties of individual fiber types, in particular in mitochondrial function. First single skeletal muscle fiber proteome, and thereby single cell proteome of any kind Single-shot proteomic analysis captures main features of type 1-slow and of the subtypes of fast fibers Qualitative differences in the mitochondrial proteome of the four fiber types uncover a metabolic specialization Here, single multinucleated muscle fibers are analyzed by high sensitivity proteomics for the first time. This reveals an unexpected diversity and specialization in metabolic properties of individual fiber types, in particular in mitochondrial function.

U2 - 10.15252/embr.201439757

DO - 10.15252/embr.201439757

M3 - Journal article

C2 - 25643707

SN - 1469-221X

VL - 16

SP - 387

EP - 395

JO - E M B O Reports

JF - E M B O Reports

IS - 3

ER -