In physiological conditions, the opening of PTPC is involved in the cardiac and neural development. The relevance of a modulation of PTPC activity in this context is supported by evidence that depletion of the main activator of the PTPC, cyclophilin D, causes cardiac myocyte differentiation to begin earlier. In pathological conditions, it has been well assessed that PTPC opening behaves as a key driver during myocardial ischemia/reperfusion (I/R) injury [10]. During ischemia cardiomyocytes are exposed to Ca2+ overload, increased oxidative stress and inflammation. These factors are known to favour the susceptibility of the PTPC to opening. In addition, once reperfusion occurs, it restores a normal pH which induces increased PTPC activity with consequent severe mitochondrial impairment and disruption of energy production, leading to a massive cellular damage. Accordingly, acidic pH reduces cell death in I/R, and this has been attributed to inhibition of the PTPC opening by acid pH. Of importance, there is evidence that inhibitors of the PTPC, i.e. cyclosporin A, may reduce infarct size following I/R in humans although a robust demonstration of this phenomenon is still lacking. The link between inhibition of the PTPC opening and cardioprotective has been demonstrated in cells, isolated hearts, and in-vivo models. Apart from the I/R and the myocardial infarct conditions, a role of PTPC opening has been hypothesized, but not yet definitively demonstrated, in heart failure.

The ATP synthase glycine zipper of the c subunits: from the structural to the functional role in mitochondrial biology of cardiovascular diseases / Nesci, Salvatore; Rubattu, Speranza. - In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. - ISSN 0167-4889. - 1868:9(2021), pp. 119075-119077. [10.1016/j.bbamcr.2021.119075]

The ATP synthase glycine zipper of the c subunits: from the structural to the functional role in mitochondrial biology of cardiovascular diseases

Rubattu, Speranza
2021

Abstract

In physiological conditions, the opening of PTPC is involved in the cardiac and neural development. The relevance of a modulation of PTPC activity in this context is supported by evidence that depletion of the main activator of the PTPC, cyclophilin D, causes cardiac myocyte differentiation to begin earlier. In pathological conditions, it has been well assessed that PTPC opening behaves as a key driver during myocardial ischemia/reperfusion (I/R) injury [10]. During ischemia cardiomyocytes are exposed to Ca2+ overload, increased oxidative stress and inflammation. These factors are known to favour the susceptibility of the PTPC to opening. In addition, once reperfusion occurs, it restores a normal pH which induces increased PTPC activity with consequent severe mitochondrial impairment and disruption of energy production, leading to a massive cellular damage. Accordingly, acidic pH reduces cell death in I/R, and this has been attributed to inhibition of the PTPC opening by acid pH. Of importance, there is evidence that inhibitors of the PTPC, i.e. cyclosporin A, may reduce infarct size following I/R in humans although a robust demonstration of this phenomenon is still lacking. The link between inhibition of the PTPC opening and cardioprotective has been demonstrated in cells, isolated hearts, and in-vivo models. Apart from the I/R and the myocardial infarct conditions, a role of PTPC opening has been hypothesized, but not yet definitively demonstrated, in heart failure.
2021
ATP synthase; amino acid mutation; c-ring; cardiovascular diseases; mitochondria; permeability transition pore complex
01 Pubblicazione su rivista::01a Articolo in rivista
The ATP synthase glycine zipper of the c subunits: from the structural to the functional role in mitochondrial biology of cardiovascular diseases / Nesci, Salvatore; Rubattu, Speranza. - In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. - ISSN 0167-4889. - 1868:9(2021), pp. 119075-119077. [10.1016/j.bbamcr.2021.119075]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1551841
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