The non-apoptotic action of Bcl-xL: regulating Ca(2+) signaling and bioenergetics at the ER-mitochondrion interface.

ABSTRACT: Bcl-2 family proteins are known to competitively regulate Ca(2+); however, the specific inter-organelle signaling pathways and related cellular functions are not fully elucidated. In this study, a portion of Bcl-xL was detected at the ER-mitochondrion interface or MAM (mitochondria-associated ER membrane) in association with type 3 inositol 1,4,5-trisphosphate receptors (IP3R3); an association facilitated by the BH4 and transmembrane domains of Bcl-xL. Moreover, increasing Bcl-xL expression enhanced transient mitochondrial Ca(2+) levels upon ER Ca(2+) depletion induced by short-term, non-apoptotic incubation with thapsigargin (Tg), while concomitantly reducing cytosolic Ca(2+) release. These mitochondrial changes appear to be IP3R3-dependent and resulted in decreased NAD/NADH ratios and hi

SUBMITTER: Williams A 

PROVIDER: S-EPMC6737942 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature