Cristae remodeling causes acidification detected by integrated graphene sensor during mitochondrial outer membrane permeabilization
View/ Open
Author
Pham, Ted D.
Pham, Phi Q.
Li, Jinfeng
Wallace, Douglas C.
Burke, Peter J.
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1038/srep35907Metadata
Show full item recordCitation
Pham, Ted D., Phi Q. Pham, Jinfeng Li, Anthony G. Letai, Douglas C. Wallace, and Peter J. Burke. 2016. “Cristae remodeling causes acidification detected by integrated graphene sensor during mitochondrial outer membrane permeabilization.” Scientific Reports 6 (1): 35907. doi:10.1038/srep35907. http://dx.doi.org/10.1038/srep35907.Abstract
The intrinsic apoptotic pathway and the resultant mitochondrial outer membrane permeabilization (MOMP) via BAK and BAX oligomerization, cytochrome c (cytc) release, and caspase activation are well studied, but their effect on cytosolic pH is poorly understood. Using isolated mitochondria, we show that MOMP results in acidification of the surrounding medium. BAK conformational changes associated with MOMP activate the OMA1 protease to cleave OPA1 resulting in remodeling of the cristae and release of the highly concentrated protons within the cristae invaginations. This was revealed by utilizing a nanomaterial graphene as an optically clear and ultrasensitive pH sensor that can measure ionic changes induced by tethered mitochondria. With this platform, we have found that activation of mitochondrial apoptosis is accompanied by a gradual drop in extra-mitochondrial pH and a decline in membrane potential, both of which can be rescued by adding exogenous cytc. These findings have importance for potential pharmacological manipulation of apoptosis, in the treatment of cancer.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081517/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:29408309
Collections
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)