Proteomics Unveils Fibroblast–Cardiomyocyte Lactate Shuttle and Hexokinase Paradox in Mouse Muscles

Abstract

Quantitative mapping, given in biochemically interpretable units such as mol per mg of total protein, of tissue-specific proteomes is prerequisite for the analysis of any process in cells. We applied label- and standard-free proteomics to characterize three types of striated muscles: white, red, and cardiac muscle. The analysis presented here uncovers several unexpected and novel features of striated muscles. In addition to differences in protein expression levels, the three muscle types substantially differ in their patterns of basic metabolic pathways and isoforms of regulatory proteins. Importantly, some of the conclusions drawn on the basis of our results, such as the potential existence of a "fibroblast-cardiomyocyte lactate shuttle" and the "hexokinase paradox" point to the necessity of reinterpretation of some basic aspects of striated muscle metabolism. The data presented here constitute a powerful database and a resource for future studies of muscle physiology and for the design of pharmaceutics for the treatment of muscular disorders.

The Reverse Warburg Effect Is Associated with Fbp2-Dependent Hif1α Regulation in Cancer Cells Stimulated by Fibroblasts

“…Together, the alteration in the cellular levels of the three proteins strongly support the hypothesis that the fibroblasts growing in the presence of cancer cells, and presumably also some other cell types (e.g., cardiomyocytes [25]), start to produce lactate while the capacity of cancer cells (and other cells which accompany fibroblasts) to produce lactate is significantly reduced.…”

Region and cell-type resolved quantitative proteomic map of the human heart

“…We calculated an approximate total protein content of 1 ng per diploid nucleus and found that a heart cavity muscle cell has an approximate volume of 5 pL per nucleus (note that about 30% of all cardiomyocytes have two or more nuclei 2 ). These values are roughly double that of mouse heart muscle cells 30 . Estimated protein copy numbers per diploid nucleus and protein concentration 31 across our samples ranged from ~10 to 10 9 and <0.1 nM to 200 µM, respectively (Supplementary Data 3 ).…”

Aging‐associated changes in hippocampal glycogen metabolism in mice. Evidence for and against astrocyte‐to‐neuron lactate shuttle

“…However, we found that the molar ratio of Pyg to Gys (a glycogen degradation to glycogen synthesis enzyme) in hippocampus is very high and similar as in white skeletal muscle fibers (Rakus, Gizak, & Wiśniewski, ), which are suited for the rapid glycogen degradation. This suggests that episodes of glycogen degradation in astrocytes are rapid and thus, the short‐time local increase in lactate may be sufficient to stimulate neuronal energy production in OXPHOS.…”

“…However, we found that the molar ratio of Pyg to Gys (a glycogen degradation to glycogen synthesis enzyme) in hippocampus is very high and similar as in white skeletal muscle fibers (Rakus, Gizak, & Wi sniewski, 2016), which are suited for the rapid glycogen degradation.…”