The mitochondrial permeability transition phenomenon elucidated by cryo-EM reveals the genuine impact of calcium overload on mitochondrial structure and function

Abstract Mitochondria have a remarkable ability to uptake and store massive amounts of calcium. However, the consequences of massive calcium accumulation remain enigmatic. In the present study, we analyzed a series of time-course experiments to identify the sequence of events that occur in a populat...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jasiel O. Strubbe-Rivera, Jason R. Schrad, Evgeny V. Pavlov, James F. Conway, Kristin N. Parent, Jason N. Bazil
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/10be602351054d3e97056f991fc7d5e6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:10be602351054d3e97056f991fc7d5e6
record_format	dspace
spelling	oai:doaj.org-article:10be602351054d3e97056f991fc7d5e62021-12-02T14:12:45ZThe mitochondrial permeability transition phenomenon elucidated by cryo-EM reveals the genuine impact of calcium overload on mitochondrial structure and function10.1038/s41598-020-80398-82045-2322https://doaj.org/article/10be602351054d3e97056f991fc7d5e62021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80398-8https://doaj.org/toc/2045-2322Abstract Mitochondria have a remarkable ability to uptake and store massive amounts of calcium. However, the consequences of massive calcium accumulation remain enigmatic. In the present study, we analyzed a series of time-course experiments to identify the sequence of events that occur in a population of guinea pig cardiac mitochondria exposed to excessive calcium overload that cause mitochondrial permeability transition (MPT). By analyzing coincident structural and functional data, we determined that excessive calcium overload is associated with large calcium phosphate granules and inner membrane fragmentation, which explains the extent of mitochondrial dysfunction. This data also reveals a novel mechanism for cyclosporin A, an inhibitor of MPT, in which it preserves cristae despite the presence of massive calcium phosphate granules in the matrix. Overall, these findings establish a mechanism of calcium-induced mitochondrial dysfunction and the impact of calcium regulation on mitochondrial structure and function.Jasiel O. Strubbe-RiveraJason R. SchradEvgeny V. PavlovJames F. ConwayKristin N. ParentJason N. BazilNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jasiel O. Strubbe-Rivera Jason R. Schrad Evgeny V. Pavlov James F. Conway Kristin N. Parent Jason N. Bazil The mitochondrial permeability transition phenomenon elucidated by cryo-EM reveals the genuine impact of calcium overload on mitochondrial structure and function
description	Abstract Mitochondria have a remarkable ability to uptake and store massive amounts of calcium. However, the consequences of massive calcium accumulation remain enigmatic. In the present study, we analyzed a series of time-course experiments to identify the sequence of events that occur in a population of guinea pig cardiac mitochondria exposed to excessive calcium overload that cause mitochondrial permeability transition (MPT). By analyzing coincident structural and functional data, we determined that excessive calcium overload is associated with large calcium phosphate granules and inner membrane fragmentation, which explains the extent of mitochondrial dysfunction. This data also reveals a novel mechanism for cyclosporin A, an inhibitor of MPT, in which it preserves cristae despite the presence of massive calcium phosphate granules in the matrix. Overall, these findings establish a mechanism of calcium-induced mitochondrial dysfunction and the impact of calcium regulation on mitochondrial structure and function.
format	article
author	Jasiel O. Strubbe-Rivera Jason R. Schrad Evgeny V. Pavlov James F. Conway Kristin N. Parent Jason N. Bazil
author_facet	Jasiel O. Strubbe-Rivera Jason R. Schrad Evgeny V. Pavlov James F. Conway Kristin N. Parent Jason N. Bazil
author_sort	Jasiel O. Strubbe-Rivera
title	The mitochondrial permeability transition phenomenon elucidated by cryo-EM reveals the genuine impact of calcium overload on mitochondrial structure and function
title_short	The mitochondrial permeability transition phenomenon elucidated by cryo-EM reveals the genuine impact of calcium overload on mitochondrial structure and function
title_full	The mitochondrial permeability transition phenomenon elucidated by cryo-EM reveals the genuine impact of calcium overload on mitochondrial structure and function
title_fullStr	The mitochondrial permeability transition phenomenon elucidated by cryo-EM reveals the genuine impact of calcium overload on mitochondrial structure and function
title_full_unstemmed	The mitochondrial permeability transition phenomenon elucidated by cryo-EM reveals the genuine impact of calcium overload on mitochondrial structure and function
title_sort	mitochondrial permeability transition phenomenon elucidated by cryo-em reveals the genuine impact of calcium overload on mitochondrial structure and function
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/10be602351054d3e97056f991fc7d5e6
work_keys_str_mv	AT jasielostrubberivera themitochondrialpermeabilitytransitionphenomenonelucidatedbycryoemrevealsthegenuineimpactofcalciumoverloadonmitochondrialstructureandfunction AT jasonrschrad themitochondrialpermeabilitytransitionphenomenonelucidatedbycryoemrevealsthegenuineimpactofcalciumoverloadonmitochondrialstructureandfunction AT evgenyvpavlov themitochondrialpermeabilitytransitionphenomenonelucidatedbycryoemrevealsthegenuineimpactofcalciumoverloadonmitochondrialstructureandfunction AT jamesfconway themitochondrialpermeabilitytransitionphenomenonelucidatedbycryoemrevealsthegenuineimpactofcalciumoverloadonmitochondrialstructureandfunction AT kristinnparent themitochondrialpermeabilitytransitionphenomenonelucidatedbycryoemrevealsthegenuineimpactofcalciumoverloadonmitochondrialstructureandfunction AT jasonnbazil themitochondrialpermeabilitytransitionphenomenonelucidatedbycryoemrevealsthegenuineimpactofcalciumoverloadonmitochondrialstructureandfunction AT jasielostrubberivera mitochondrialpermeabilitytransitionphenomenonelucidatedbycryoemrevealsthegenuineimpactofcalciumoverloadonmitochondrialstructureandfunction AT jasonrschrad mitochondrialpermeabilitytransitionphenomenonelucidatedbycryoemrevealsthegenuineimpactofcalciumoverloadonmitochondrialstructureandfunction AT evgenyvpavlov mitochondrialpermeabilitytransitionphenomenonelucidatedbycryoemrevealsthegenuineimpactofcalciumoverloadonmitochondrialstructureandfunction AT jamesfconway mitochondrialpermeabilitytransitionphenomenonelucidatedbycryoemrevealsthegenuineimpactofcalciumoverloadonmitochondrialstructureandfunction AT kristinnparent mitochondrialpermeabilitytransitionphenomenonelucidatedbycryoemrevealsthegenuineimpactofcalciumoverloadonmitochondrialstructureandfunction AT jasonnbazil mitochondrialpermeabilitytransitionphenomenonelucidatedbycryoemrevealsthegenuineimpactofcalciumoverloadonmitochondrialstructureandfunction
_version_	1718391768241668096

The mitochondrial permeability transition phenomenon elucidated by cryo-EM reveals the genuine impact of calcium overload on mitochondrial structure and function

Ejemplares similares