Myoglobin, expressed in brown adipose tissue of mice, regulates the content and activity of mitochondria and lipid droplets

Aboouf, Mostafa A.; Armbruster, Julia; Thiersch, Markus; Gassmann, Max; Gödecke, Axel; Gnaiger, Erich; Kristiansen, Glen; Bicker, Anne; Hankeln, Thomas; Zhu, Hao; Gorr, Thomas A.

doi:10.1016/j.bbalip.2021.159026

Cited by 16 publications

(59 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ectopic occurrence of Mb isoforms in tissues different from skeletal/myocardial muscle was first reported in the liver and other organs of hypoxia-tolerant fish models [ 27 – 29 ]. More recently, Mb was found to be expressed in several cancer cell lines and epithelial tumors [ 7 , 30 , 31 ] and in mice brown adipose tissue [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…Of relevance in the context of what above discussed is the reported evidence that Mb in its oxygenated form can bind fatty acids with affinity constants in the micromolar range and therefore compatible with physiological conditions [ 72 – 75 ] (see graphical abstract). Accordingly, brown adipose tissue of Mb knockout mice exhibits dysregulation of lipid homeostasis, with reduced mitochondrial density and respiratory activity [ 32 ]. All this would support the proposal that Mb might function as a transporter of fatty acid to be released to mitochondria and might account for the here-reported different levels of co-localization of Mb with mitochondria in PAM-MSCs and MAT-MSCs.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Myoglobin expression by alternative transcript in different mesenchymal stem cells compartments

et al. 2022

View full text Add to dashboard Cite

Background The metabolic phenotype of stem cells is increasingly recognized as a hallmark of their pluripotency with mitochondrial and oxygen-related metabolism playing a not completely defined role in this context. In a previous study, we reported the ectopic expression of myoglobin (MB) in bone marrow-derived hematopoietic stem/progenitor cells. Here, we have extended the analysis to mesenchymal stem cells (MSCs) isolated from different tissues. Methods MSCs were isolated from human placental membrane, mammary adipose tissue and dental pulp and subjected to RT-PCR, Western blotting and mass spectrometry to investigate the expression of MB. A combination of metabolic flux analysis and cyto-imaging was used to profile the metabolic phenotype and the mitochondria dynamics in the different MSCs. Results As for the hematopoietic stem/progenitor cells, the expression of Mb was largely driven by an alternative transcript with the protein occurring both in the monomer and in the dimer forms as confirmed by mass spectrometry analysis. Comparing the metabolic fluxes between neonatal placental membrane-derived and adult mammary adipose tissue-derived MSCs, we showed a significantly more active bioenergetics profile in the former that correlated with a larger co-localization of myoglobin with the mitochondrial compartment. Differences in the structure of the mitochondrial network as well as in the expression of factors controlling the organelle dynamics were also observed between neonatal and adult mesenchymal stem cells. Finally, the expression of myoglobin was found to be strongly reduced following osteogenic differentiation of dental pulp-derived MSCs, while it was upregulated following reprogramming of human fibroblasts to induce pluripotent stem cells. Conclusions Ectopic expression of myoglobin in tissues other than muscle raises the question of understanding its function therein. Properties in addition to the canonical oxygen storage/delivery have been uncovered. Finding of Mb expressed via an alternative gene transcript in the context of different stem cells with metabolic phenotypes, its loss during differentiation and recovery in iPSCs suggest a hitherto unappreciated role of Mb in controlling the balance between aerobic metabolism and pluripotency. Understanding how Mb contributes through modulation of the mitochondrial physiology to the stem cell biology paves the way to novel perspectives in regenerative medicine as well as in cancer stem cell therapy. Graphical abstract

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Myoglobin expression by alternative transcript in different mesenchymal stem cells compartments

et al. 2022

View full text Add to dashboard Cite

show abstract

“…As in human skeletal muscle cells [ 14 ], CqGPx3b levels may have important implications for the regeneration of Pe muscle. In a GPx3 similar response of iBAT MBko mice [ 17 ], it is possible that GPx3b in NC and Pe of C. quadricarinatus under hypoxic conditions could be related to an ATP production diminishment strategy. Multiple peroxidases regulation patterns are known.…”

Section: Discussionmentioning

confidence: 99%

“…Under these circumstances, GPx3 expression rose 4.5-fold [ 16 ]. In the butterfly-shaped interscapular brown adipose tissue (iBAT) of myoglobin knockout (MBko) mice, GPx3 expression decreased significantly compared to the wild type, indicating anoxia-related diminishment of H 2 O 2 and a ATP synthesis decrease [ 17 ]. Variants or isoforms of GPx3 have been reported in differential expression patterns.…”

Section: Introductionmentioning

confidence: 99%

cDNA Characterization and Expression of Selenium-Dependent CqGPx3 Isoforms in the Crayfish Cherax quadricarinatus under High Temperature and Hypoxia

Hernández-Aguirre

Fuentes-Sidas

Rivera-Rangel

et al. 2022

Genes

View full text Add to dashboard Cite

Glutathione peroxidase 3 (GPx3) is the only extracellular selenoprotein (Sel) that enzymatically reduces H2O2 to H2O and O2. Two GPx3 (CqGPx3) cDNAs were characterized from crayfish Cherax quadricarinatus. The nerve cord CqGPx3a isoform encodes for a preprotein containing an N-terminal signal peptide of 32 amino acid residues, with the mature Sel region of 192 residues and a dispensable phosphorylation domain of 36 residues. In contrast, the pereiopods CqGPx3b codes for a precursor protein with 19 residues in the N-terminal signal peptide, then the mature 184 amino acid residues protein and finally a Pro-rich peptide of 42 residues. CqGPx3 are expressed in cerebral ganglia, pereiopods and nerve cord. CqGPx3a is expressed mainly in cerebral ganglia, antennulae and nerve cord, while CqGPx3b was detected mainly in pereiopods. CqGPx3a expression increases with high temperature and hypoxia; meanwhile, CqGPx3b is not affected. We report the presence and differential expression of GPx3 isoforms in crustacean tissues in normal conditions and under stress for high temperature and hypoxia. The two isoforms are tissue specific and condition specific, which could indicate an important role of CqGPx3a in the central nervous system and CqGPx3b in exposed tissues, both involved in different responses to environmental stressors.

show abstract

“…When stimulated by external cues such as exercise and contraction, beige adipocytes express UCP1 protein and exhibit UCP1-dependent thermogenic capacity [24,53]. Moreover, IL-6 has a dual role: as a major myokine, it activates beige adipocyte development and is required for exercise-induced white adipose tissue browning in mice [54]; as an adipokine, IL-6 acts as a mediator in non-shivering thermogenesis and is involved in metabolic profile regulation in mice [55,56]. In line with these findings, we detected a significantly higher expression of UCP1 in 3T3-L1 adipocytes co-cultured with C2C12 myotubes under the effect of muscle contraction, in comparison to the non-co-cultured adipocytes.…”

Section: Discussionmentioning

confidence: 99%

Effects of In Vitro Muscle Contraction on Thermogenic Protein Levels in Co-Cultured Adipocytes

Nintou

Karligiotou

Vliora

et al. 2021

Life

View full text Add to dashboard Cite

The crosstalk between the exercising muscle and the adipose tissue, mediated by myokines and metabolites, derived from both tissues during exercise has created a controversy between animal and human studies with respect to the impact of exercise on the browning process. The aim of this study was to investigate whether co-culturing of C2C12 myotubes and 3T3-L1 adipocytes under the stimuli of electrical pulse stimulation (EPS) mimicking muscle contraction can impact the expression of UCP1, PGC-1a, and IL-6 in adipocytes, therefore providing evidence on the direct crosstalk between adipocytes and stimulated muscle cells. In the co-cultured C2C12 cells, EPS increased the expression of PGC-1a (p = 0.129; d = 0.73) and IL-6 (p = 0.09; d = 1.13) protein levels. When EPS was applied, we found that co-culturing led to increases in UCP1 (p = 0.044; d = 1.29) and IL-6 (p = 0.097; d = 1.13) protein expression in the 3T3-L1 adipocytes. The expression of PGC-1a increased by EPS but was not significantly elevated after co-culturing (p = 0.448; d = 0.08). In vitro co-culturing of C2C12 myotubes and 3T3-L1 adipocytes under the stimuli of EPS leads to increased expression of thermogenic proteins. These findings indicate changes in the expression pattern of proteins related to browning of adipose tissue, supporting the use of this in vitro model to study the crosstalk between adipocytes and contracting muscle.

show abstract

Myoglobin, expressed in brown adipose tissue of mice, regulates the content and activity of mitochondria and lipid droplets

Cited by 16 publications

References 90 publications

Myoglobin expression by alternative transcript in different mesenchymal stem cells compartments

Myoglobin expression by alternative transcript in different mesenchymal stem cells compartments

cDNA Characterization and Expression of Selenium-Dependent CqGPx3 Isoforms in the Crayfish Cherax quadricarinatus under High Temperature and Hypoxia

Effects of In Vitro Muscle Contraction on Thermogenic Protein Levels in Co-Cultured Adipocytes

Contact Info

Product

Resources

About