Proteomic Analysis Reveals a Mitochondrial Remodeling of βTC3 Cells in Response to Nanotopography

Maffioli, Elisa; Galli, A.; Nonnis, Simona; Marku, A.; Negri, Armando; Piazzoni, Claudio; Milani, Paolo; Lenardi, Cristina; Perego, Carla; Tedeschi, Gioacchino

doi:10.3389/fcell.2020.00508

Cited by 12 publications

(11 citation statements)

References 45 publications

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“…A high number of identified proteins (270 out of 397; 68) were classified as known or predicted to be mitochondrial proteins. The mitochondrial enrichment procedure applied to increase mitochondrial protein abundance exhibited an efficiency comparable to that observed in other studies (Alberio et al, 2017;Maffioli et al, 2020). The presence of non-mitochondrial proteins (i.e., endoplasmic reticulum, cytoskeletal proteins) is due to the physical connection between the mitochondria and other subcellular organelles (Dolman et al, 2005;Rowland and Voeltz, 2012;Xia et al, 2019;Giacomello et al, 2020) as already demonstrated in previous studies (Rezaul et al, 2005;Alberio et al, 2017;Chae et al, 2018).…”

Section: Shotgun Proteomics Analysis Reveals Changes In Mitochondrialsupporting

confidence: 77%

Relationship Between Mitochondrial Structure and Bioenergetics in Pseudoxanthoma elasticum Dermal Fibroblasts

Lofaro

Boraldi

García-Fernández

et al. 2020

Front. Cell Dev. Biol.

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Pseudoxanthoma elasticum (PXE) is a genetic disease considered as a paradigm of ectopic mineralization disorders, being characterized by multisystem clinical manifestations due to progressive calcification of skin, eyes, and the cardiovascular system, resembling an age-related phenotype. Although fibroblasts do not express the pathogenic ABCC6 gene, nevertheless these cells are still under investigation because they regulate connective tissue homeostasis, generating the “arena” where cells and extracellular matrix components can promote pathologic calcification and where activation of pro-osteogenic factors can be associated to pathways involving mitochondrial metabolism. The aim of the present study was to integrate structural and bioenergenetic features to deeply investigate mitochondria from control and from PXE fibroblasts cultured in standard conditions and to explore the role of mitochondria in the development of the PXE fibroblasts’ pathologic phenotype. Proteomic, biochemical, and morphological data provide new evidence that in basal culture conditions (1) the protein profile of PXE mitochondria reveals a number of differentially expressed proteins, suggesting changes in redox balance, oxidative phosphorylation, and calcium homeostasis in addition to modified structure and organization, (2) measure of oxygen consumption indicates that the PXE mitochondria have a low ability to cope with a sudden increased need for ATP via oxidative phosphorylation, (3) mitochondrial membranes are highly polarized in PXE fibroblasts, and this condition contributes to increased reactive oxygen species levels, (4) ultrastructural alterations in PXE mitochondria are associated with functional changes, and (5) PXE fibroblasts exhibit a more abundant, branched, and interconnected mitochondrial network compared to control cells, indicating that fusion prevail over fission events. In summary, the present study demonstrates that mitochondria are modified in PXE fibroblasts. Since mitochondria are key players in the development of the aging process, fibroblasts cultured from aged individuals or aged in vitro are more prone to calcify, and in PXE, calcified tissues remind features of premature aging syndromes; it can be hypothesized that mitochondria represent a common link contributing to the development of ectopic calcification in aging and in diseases. Therefore, ameliorating mitochondrial functions and cell metabolism could open new strategies to positively regulate a number of signaling pathways associated to pathologic calcification.

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Section: Shotgun Proteomics Analysis Reveals Changes In Mitochondrialsupporting

confidence: 77%

Relationship Between Mitochondrial Structure and Bioenergetics in Pseudoxanthoma elasticum Dermal Fibroblasts

Lofaro

Boraldi

García-Fernández

et al. 2020

Front. Cell Dev. Biol.

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“…We found that the extracellular matrix nanotopography, via a mechanotransduction pathway which involves mechanosensitive integrins, reorganisation of the actin cytoskeleton and changes in the nuclear architecture, triggers a specific transcriptional program necessary for the metabolic adaptation of cells to the new environment. This response is mediated by modifications of the mitochondrial activity and dynamics and involves the crosstalk of mitochondria with other organelles as lysosomes and ER, where iron exchange takes place [ 72 , 74 , 79 , 112 ], also envisioning a possible role of iron in this signalling.…”

Section: Iron Is Required For the Normal Beta-cell Functionmentioning

confidence: 99%

Iron Metabolism in Pancreatic Beta-Cell Function and Dysfunction

Marku

Galli

Marciani

et al. 2021

Cells

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Iron is an essential element involved in a variety of physiological functions. In the pancreatic beta-cells, being part of Fe-S cluster proteins, it is necessary for the correct insulin synthesis and processing. In the mitochondria, as a component of the respiratory chain, it allows the production of ATP and reactive oxygen species (ROS) that trigger beta-cell depolarization and potentiate the calcium-dependent insulin release. Iron cellular content must be finely tuned to ensure the normal supply but also to prevent overloading. Indeed, due to the high reactivity with oxygen and the formation of free radicals, iron excess may cause oxidative damage of cells that are extremely vulnerable to this condition because the normal elevated ROS production and the paucity in antioxidant enzyme activities. The aim of the present review is to provide insights into the mechanisms responsible for iron homeostasis in beta-cells, describing how alteration of these processes has been related to beta-cell damage and failure. Defects in iron-storing or -chaperoning proteins have been detected in diabetic conditions; therefore, the control of iron metabolism in these cells deserves further investigation as a promising target for the development of new disease treatments.

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“…The supernatant containing peptides and low-molecular-weight proteins were collected, dried (Speed Vacuum), dissolved in 1% (v/v) formic acid, and desalted (Zip-Tip C18, Millipore) before mass spectrometric (MS) analysis. MS/MS analysis was carried out by a Orbitrap Fusion Tribrid mass spectrometer (Thermo Fisher Sci., Waltham, MA, USA), as previously described [ 39 ]. Data Base search was performed using the Sequest search engine of Proteome Discoverer 1.4 (Thermo Fisher Sci.)…”

Section: Methodsmentioning

confidence: 99%

Antimicrobial d-amino acid oxidase-derived peptides specify gut microbiota

Murtas

Sacchi

Tedeschi

et al. 2021

Cell. Mol. Life Sci.

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The flavoenzyme d-amino acid oxidase (DAAO) is deputed to the degradation of d-enantiomers of amino acids. DAAO plays various relevant physiological roles in different organisms and tissues. Thus, it has been recently suggested that the goblet cells of the mucosal epithelia secrete into the lumen of intestine, a processed and active form of DAAO that uses the intestinal d-amino acids to generate hydrogen peroxide (H2O2), an immune messenger that helps fighting gut pathogens, and by doing so controls the homeostasis of gut microbiota. Here, we show that the DAAO form lacking the 1–16 amino acid residues (the putative secretion signal) is unstable and inactive, and that DAAO is present in the epithelial layer and the mucosa of mouse gut, where it is largely proteolyzed. In silico predicted DAAO-derived antimicrobial peptides show activity against various Gram-positive and Gram-negative bacteria but not on Lactobacilli species, which represent the commensal microbiota. Peptidomic analysis reveals the presence of such peptides in the mucosal fraction. Collectively, we identify a novel mechanism for gut microbiota selection implying DAAO-derived antimicrobial peptides which are generated by intestinal proteases and that are secreted in the gut lumen. In conclusion, we herein report an additional, ancillary role for mammalian DAAO, unrelated to its enzymatic activity.

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Proteomic Analysis Reveals a Mitochondrial Remodeling of βTC3 Cells in Response to Nanotopography

Cited by 12 publications

References 45 publications

Relationship Between Mitochondrial Structure and Bioenergetics in Pseudoxanthoma elasticum Dermal Fibroblasts

Relationship Between Mitochondrial Structure and Bioenergetics in Pseudoxanthoma elasticum Dermal Fibroblasts

Iron Metabolism in Pancreatic Beta-Cell Function and Dysfunction

Antimicrobial d-amino acid oxidase-derived peptides specify gut microbiota

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