@article{607c2d6d4c2248af8a2723fba44cdbba,
title = "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 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.",
author = "Strubbe-Rivera, {Jasiel O.} and Schrad, {Jason R.} and Pavlov, {Evgeny V.} and Conway, {James F.} and Parent, {Kristin N.} and Bazil, {Jason N.}",
note = "Funding Information: The authors thank Dr. Sundharraman Subramanian of Michigan State University (MSU), MI and Dr. Alexander Makhov of University of Pittsburgh, PA for technical support with cryo-electron microscopy. This work was supported by the MSU RTSF Cryo-EM Facility. This work was also supported in part by the Office of the Director, National Institutes of Health, under Award Number S10 OD019995 (JFC), and the National Institutes of Health Grants R00-HL121160 (JNB) and F31-HL121160 (JOSR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The AAAS Marion Mason Milligan award provided funding for this project for Women in the Chemical Sciences, the JK Billman, Jr., MD Endowed Research Professorhip, and NIH R01 GM110185 (KNP).",
year = "2021",
month = dec,
doi = "10.1038/s41598-020-80398-8",
language = "English (US)",
volume = "11",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}