C subunit of the ATP synthase is an amyloidogenic calcium dependent channel-forming peptide with possible implications in mitochondrial permeability transition

Abstract The c subunit is an inner mitochondrial membrane (IMM) protein encoded by three nuclear genes. Best known as an integral part of the F0 complex of the ATP synthase, the c subunit is also present in other cytoplasmic compartments in ceroid lipofuscinoses. Under physiological conditions, this...

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Autores principales:	Giuseppe Federico Amodeo, Brenda Yasie Lee, Natalya Krilyuk, Carina Teresa Filice, Denis Valyuk, Daniel Erik Otzen, Sergey Noskov, Zoya Leonenko, Evgeny V. Pavlov
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b00333c6b7dd491981fe6f05f6206b8b
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spelling	oai:doaj.org-article:b00333c6b7dd491981fe6f05f6206b8b2021-12-02T17:32:59ZC subunit of the ATP synthase is an amyloidogenic calcium dependent channel-forming peptide with possible implications in mitochondrial permeability transition10.1038/s41598-021-88157-z2045-2322https://doaj.org/article/b00333c6b7dd491981fe6f05f6206b8b2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88157-zhttps://doaj.org/toc/2045-2322Abstract The c subunit is an inner mitochondrial membrane (IMM) protein encoded by three nuclear genes. Best known as an integral part of the F0 complex of the ATP synthase, the c subunit is also present in other cytoplasmic compartments in ceroid lipofuscinoses. Under physiological conditions, this 75 residue-long peptide folds into an α-helical hairpin and forms oligomers spanning the lipid bilayer. In addition to its physiological role, the c subunit has been proposed as a key participant in stress-induced IMM permeabilization by the mechanism of calcium-induced permeability transition. However, the molecular mechanism of the c subunit participation in IMM permeabilization is not completely understood. Here we used fluorescence spectroscopy, atomic force microscopy and black lipid membrane methods to gain insights into the structural and functional properties of unmodified c subunit protein that might make it relevant to mitochondrial toxicity. We discovered that c subunit is an amyloidogenic peptide that can spontaneously fold into β-sheets and self-assemble into fibrils and oligomers in a Ca2+-dependent manner. C subunit oligomers exhibited ion channel activity in lipid membranes. We propose that the toxic effects of c subunit might be linked to its amyloidogenic properties and are driven by mechanisms similar to those of neurodegenerative polypeptides such as Aβ and α-synuclein.Giuseppe Federico AmodeoBrenda Yasie LeeNatalya KrilyukCarina Teresa FiliceDenis ValyukDaniel Erik OtzenSergey NoskovZoya LeonenkoEvgeny V. PavlovNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Giuseppe Federico Amodeo Brenda Yasie Lee Natalya Krilyuk Carina Teresa Filice Denis Valyuk Daniel Erik Otzen Sergey Noskov Zoya Leonenko Evgeny V. Pavlov C subunit of the ATP synthase is an amyloidogenic calcium dependent channel-forming peptide with possible implications in mitochondrial permeability transition
description	Abstract The c subunit is an inner mitochondrial membrane (IMM) protein encoded by three nuclear genes. Best known as an integral part of the F0 complex of the ATP synthase, the c subunit is also present in other cytoplasmic compartments in ceroid lipofuscinoses. Under physiological conditions, this 75 residue-long peptide folds into an α-helical hairpin and forms oligomers spanning the lipid bilayer. In addition to its physiological role, the c subunit has been proposed as a key participant in stress-induced IMM permeabilization by the mechanism of calcium-induced permeability transition. However, the molecular mechanism of the c subunit participation in IMM permeabilization is not completely understood. Here we used fluorescence spectroscopy, atomic force microscopy and black lipid membrane methods to gain insights into the structural and functional properties of unmodified c subunit protein that might make it relevant to mitochondrial toxicity. We discovered that c subunit is an amyloidogenic peptide that can spontaneously fold into β-sheets and self-assemble into fibrils and oligomers in a Ca2+-dependent manner. C subunit oligomers exhibited ion channel activity in lipid membranes. We propose that the toxic effects of c subunit might be linked to its amyloidogenic properties and are driven by mechanisms similar to those of neurodegenerative polypeptides such as Aβ and α-synuclein.
format	article
author	Giuseppe Federico Amodeo Brenda Yasie Lee Natalya Krilyuk Carina Teresa Filice Denis Valyuk Daniel Erik Otzen Sergey Noskov Zoya Leonenko Evgeny V. Pavlov
author_facet	Giuseppe Federico Amodeo Brenda Yasie Lee Natalya Krilyuk Carina Teresa Filice Denis Valyuk Daniel Erik Otzen Sergey Noskov Zoya Leonenko Evgeny V. Pavlov
author_sort	Giuseppe Federico Amodeo
title	C subunit of the ATP synthase is an amyloidogenic calcium dependent channel-forming peptide with possible implications in mitochondrial permeability transition
title_short	C subunit of the ATP synthase is an amyloidogenic calcium dependent channel-forming peptide with possible implications in mitochondrial permeability transition
title_full	C subunit of the ATP synthase is an amyloidogenic calcium dependent channel-forming peptide with possible implications in mitochondrial permeability transition
title_fullStr	C subunit of the ATP synthase is an amyloidogenic calcium dependent channel-forming peptide with possible implications in mitochondrial permeability transition
title_full_unstemmed	C subunit of the ATP synthase is an amyloidogenic calcium dependent channel-forming peptide with possible implications in mitochondrial permeability transition
title_sort	c subunit of the atp synthase is an amyloidogenic calcium dependent channel-forming peptide with possible implications in mitochondrial permeability transition
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b00333c6b7dd491981fe6f05f6206b8b
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C subunit of the ATP synthase is an amyloidogenic calcium dependent channel-forming peptide with possible implications in mitochondrial permeability transition

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