@article{c4c2e6489de74c9f954b6d1fbe4d0778,
title = "Mitochondrial shape governs BAX-induced membrane permeabilization and apoptosis",
abstract = "Proapoptotic BCL-2 proteins converge upon the outer mitochondrial membrane (OMM) to promote mitochondrial outer membrane permeabilization (MOMP) and apoptosis. Here we investigated the mechanistic relationship between mitochondrial shape and MOMP and provide evidence that BAX requires a distinct mitochondrial size to induce MOMP. We utilized the terminal unfolded protein response pathway to systematically define proapoptotic BCL-2 protein composition after stress and then directly interrogated their requirement for a productive mitochondrial size. Complementary biochemical, cellular, invivo, and exvivo studies reveal that Mfn1, a GTPase involved in mitochondrial fusion, establishes a mitochondrial size that is permissive for proapoptotic BCL-2 family function. Cells with hyperfragmented mitochondria, along with size-restricted OMM model systems, fail to support BAX-dependent membrane association and permeabilization due to an inability to stabilize BAXα9·membrane interactions. This work identifies a mechanistic contribution of mitochondrial size in dictating BAX activation, MOMP, and apoptosis.",
author = "Renault, {Thibaud T.} and Floros, {Konstantinos V.} and Rana Elkholi and Corrigan, {Kelly Ann} and Yulia Kushnareva and Wieder, {Shira Y.} and Claudia Lindtner and Serasinghe, {Madhavika N.} and Asciolla, {James J.} and Christoph Buettner and Newmeyer, {Donald D.} and Chipuk, {Jerry E.}",
note = "Funding Information: We would like to thank everyone in the Chipuk Laboratory for their assistance and support. This work was supported by the following: NIH grants CA157740 (to J.E.C.), DK074873 (to C.B.), DK083568 (to C.B.), and DK082724 (to C.B.); a pilot project from NIH P20AA017067 (to J.E.C.), the JJR Foundation (to J.E.C.), the William A. Spivak Fund (to J.E.C.), the Fridolin Charitable Trust (to J.E.C.), and an American Cancer Society Research Scholar Award (to J.E.C.); and an ADA career development award (to C.B.). This work was also supported in part by two research grants (5-FY11-74 and 1-FY13-416) from the March of Dimes Foundation (to J.E.C.), an Albert Einstein Research Fellowship (to S.Y.W.), an American Skin Association Medical Students Grant (to S.Y.W.), and the Developmental Research Pilot Project Program within the Department of Oncological Sciences at Mount Sinai (to J.E.C.). Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = jan,
day = "8",
doi = "10.1016/j.molcel.2014.10.028",
language = "English (US)",
volume = "57",
pages = "69--82",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "1",
}