title: Inter-organellar communication with mitochondria regulates both the intrinsic and extrinsic pathways of apoptosis.
abstract: One of our major research interests is to define BCL-2 family function in the cellular decision to induce mitochondrial outer membrane permeabilization and apoptosis. Curiosity in BCL-2 family - mitochondrial interactions led to the identification that the sphingolipid pathway plays a crucial role in BCL-2 family function. For approximately 20 years, sphingolipid biology and apoptotic mechanisms have criss-crossed, but remained distinct, as neither literature could explain the observable interplay between these pathways. We recently identified that two products within the sphingolipid pathway, sphingosine-1-PO4 and hexadecenal, directly regulate BAK and BAX activation, respectively. Furthermore, our work suggests that mitochondrial communication with heterotypic membrane and/or organelles may be an important regulatory mechanism for apoptotic sensitivity.
authors.affiliation: Department of Oncological Sciences; Mount Sinai School of Medicine; New York, NY USA ; The Tisch Cancer Institute; New York, NY USA.
authors.forename: Thibaud T
authors.initials: TT
authors.lastname: Renault
authors.forename: Jerry E
authors.initials: JE
authors.lastname: Chipuk
keywords: BCL-2 family; apoptosis; cytochrome c release; endoplasmic reticulum; mitochondria; organelles; sphingolipids